食管鳞癌酪氨酸磷酸化蛋白质组学分析及MYH9 SiRNA对食管鳞癌细胞生物学行为的影响
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摘要
研究背景及目的食管癌的死亡率在我国恶性肿瘤中居第四位,超过90%的食管癌患者是鳞状细胞癌。由于大多数食管癌患者就诊时已处于晚期,因此采用手术切除为主的综合治疗,其5年生存率仍然很低。研究表明,酪氨酸激酶信号通路在多种肿瘤中表达异常,但是由于酪氨酸磷酸化蛋白质在组织中的丰度很低,目前尚无对食管鳞癌及癌旁正常食管组织(简称癌旁组织,下同)进行酪氨酸磷酸化蛋白质组学的研究。本实验采用新的酪氨酸磷酸化蛋白质组分析方法,对食管鳞癌及癌旁组织进行差异性酪氨酸磷酸化蛋白质组学研究,为揭示酪氨酸激酶信号通路在食管鳞癌发生、发展中的作用提供依据,同时为食管鳞癌的治疗及早期诊断研究开辟新的思路。
方法在第一章中我们收集了28对食管鳞癌及癌旁组织标本,采用酪氨酸磷酸化抗体免疫沉淀富集酪氨酸磷酸化多肽,并用LTQ Orbitrap质谱仪进行鉴定,将鉴定结果导入Genepattern软件进行分析,筛选出差异明显的酪氨酸磷酸化蛋白质,其中酪氨酸磷酸化差异最为明显的MYH9(编码NMIIA蛋白),其与DDR1关系密切。
在第二章中我们提取了MYH9磷酸化水平最高的10例食管鳞癌组织基因组DNA,经PCR和测序检测了MYH9基因是否存在相关位点突变,western blot验证了NMⅡA蛋白在28对食管鳞癌和癌旁组织中的表达差异,采用免疫组织化学的方法研究了50例食管鳞癌组织和30例癌旁组织中NMⅡA和DDR1的表达,并与临床病理资料进行相关性分析。
在第三章中我们检测了3株食管鳞癌细胞株KYSE-140、KYSE-150、KYSE-510的酪氨酸磷酸化蛋白质谱,比较了人食管鳞癌组织和鳞癌细胞株酪氨酸磷酸化蛋白质表达的差异,同时为第四章进行NMⅡA蛋白的功能学研究提供细胞依据。
在第四章中,我们应用SiRNA沉默MYH9基因,qRT-PCR和westernblot检测SiRNA对NMⅡA蛋白的沉默水平,细胞计数明确NMⅡA蛋白沉默对细胞增殖能力的影响,细胞粘附实验检测NMⅡA蛋白沉默对细胞粘附能力的影响,划痕试验和transwell实验评价NMⅡA蛋白沉默对细胞的平面和3-D迁移能力的影响。
结果
1.在28对食管鳞癌及癌旁组织中共检测到1037种差异性酪氨酸磷酸化蛋白质,其中有477种在鳞癌组织中上调,560种在癌旁组织中上调。在肿瘤组织中酪氨酸磷酸化水平最高的是MYH9, palladin, APP, DDR1, K105种蛋白,在癌旁组织中酪氨酸磷酸化水平最高的是K23,K20, Sciellin, envoplakin, EphA15种蛋白。食管鳞癌及癌旁组织中总体酪氨酸磷酸化蛋白质无明显差异。MYH9的酪氨酸磷酸化位点是Tyr754和Tyr1408。经相关分析,MYH9与DDR1的关系密切。
2.测序结果显示MYH9基因的1,10,16,24-26,30-32,35-39等14个外显子没有检测到常见突变位点。Western blot检测表明NMⅡA蛋白在28对肿瘤组织中的表达高于癌旁组织。免疫组化显示,NMⅡA蛋白在所有的食管鳞癌组织中表达,显著高于癌旁组织(100% VS 26.7%,P=O.000),其中强阳性表达25例(50%),NMⅡA的强阳性表达与肿瘤的侵润深度无关,与淋巴结转移个数、组织学分级相关,随着转移淋巴结个数增加,NMⅡA强阳性表达率明显增加(P=0.015<0.05),低分化组病例的强阳性表达率也显著高于高分化组(P=0.018<0.05)；DDR1蛋白在肿瘤组织中阳性率显著高于癌旁组织中的阳性率(86% VS30%,P=0.000),DDR1的表达仅与肿瘤的侵润深度有关(P=0.027<0.05),与转移淋巴结个数和肿瘤组织分化程度无关。
3.食管鳞癌细胞株中的酪氨酸磷酸化蛋白质类型和磷酸化水平与鳞癌组织中的磷酸化类型和水平存在明显差异；在3株食管鳞癌细胞株中,只有KYSE-510发生了动力/收缩蛋白的酪氨酸磷酸化,并且磷酸化的动力/收缩蛋白只有KLC2, MYH9和dnnactin2三种。三株细胞株中均有NMⅡA蛋白的表达,KYSE-140的表达相对较低。
4. Western blot检测结果显示基因沉默效率在72h SiRNA/转染试剂比例为75ng/1.5ul时最高,qRT-PCR检测提示MYH9 mRNA被SiRNA沉默了89.9%,应用MYH9 SiRNA沉默KYSE-510细胞NMⅡA蛋白表达后,与阴性转染组相比,细胞的增殖速度减慢,体外粘附实验显示细胞的粘附能力增强,细胞的平面和3-D迁移能力降低(P<0.01)。
结论
1.应用PhosphoScan技术对食管鳞癌及癌旁组织进行了酪氨酸磷酸化蛋白质组学分析,筛选出了多个在食管鳞癌中酪氨酸磷酸化异常增高的蛋白质,最明显的是动力/收缩蛋白NMⅡA和受体型酪氨酸激酶DDR1；
2.食管鳞癌组织中NMⅡA的高酪氨酸磷酸化可能不是由MYH9基因突变引起,而是与组织中NMⅡA蛋白的表达量增高有关；
3.食管鳞癌组织中NMⅡA的高表达与食管鳞癌组织的分化和转移有关；DDR1蛋白的高表达只与食管鳞癌组织的侵袭性有关。
4. KYSE-510细胞表达NMⅡA蛋白和酪氨酸磷酸化NMⅡA；
5.采用SiRNA沉默MYH9基因抑制细胞内NMⅡA的表达后抑制了KYSE-510细胞的迁移和增殖能力但增强了粘附能力。
Background and purpose Esophageal cancer is the fourth most common malignancies in China and more than 90% patients are squamous cell carcinoma. Owing to the advanced stage when patients are examined, the 5-year survival rate is still low although they might receive comprehensive treatment including operation. Recently, abnormal expression of tyrosine kinase signaling pathway has been found in many tumors by some researchers, however, tyrosine phosphorylation is at low abundance in tissues. Hence there was no tyrosine phospho-proteomics research on esophageal cancer yet. Here, we investigated differential protein tyrosine phosphorylation between esophageal cancer and para-esophageal cancer normal tissues (simply, para-cancer tissues) with a new tyrosine phospho-proteomics method. This study would provide basic proof for understanding the role of tyrosine kinase signaling in the occurrence and development of esophageal cancer, and also offer new insights into the treatment and early diagnosis of esophageal cancer.
Methods In the first chapter, we collected 28 cases of esophageal squamous cancer and corresponding para-cancer tissues. Tyrosine phosphorylated peptides were enriched by immunoaffinity purification, and analyzed by LTQ Orbitrap mass spectrometer. Differential phosphorylated proteins were analyzed by using Genepattern software. MYH9 (encoding NMⅡA) was the top phosphorylated protein between the cancer and para-cancer group and was closely correlated with DDR1.
In the second chapter, we extracted genomic DNA from ten cancer tissues with highest MYH9 phosphorylation and sequenced PCR products to find any mutations of MYH9. Western blot was adopted to validate NMⅡA expression in the 28 pair specimen. Another 50 cancer specimen and 30 para-cancer normal specimen were chosen to investigate the expression of NMⅡA and DDR1 using immunohistochemistry (IHC) and correlations between their expressions and patients'clinical data were also analyzed.
In chapter three, we cultured and profiled three esophageal squamous cancer cell lines(KYSE-140、KYSE-150、KYSE-510) by mass spectrometer. Comparison of primary human esophageal cancer and cancer cell lines was made and suggested that cell lines can be used as models to validate targets identified in primary tumors.
In the fourth chapter, we silenced MYH9 with small interfering RNA; qRT-PCR and western blot were used to study the silence effect. We counted cell number to find any effect of decreased NMⅡA on cell proliferation. Cell adhesion assay was used to analyze the effect of decreased NMⅡA on cell adhesion ability. Wound closure assay and transwell assay were used to assess the effect of decreased NMⅡA on cell migration ability.
Results
1. In this study, we identified 1037 tyrosine phosphorylated proteins. 477 of them were enriched in cancers while 560 were enriched in para-cancer tissues. The top 5 tyrosine phosphorylated proteins were MYH9, palladin, APP, DDR1 and K10 in the cancer group and K23, K20, Sciellin, envoplakin and EphA1 in para-cancer group. No significant difference of tyrosine phosphorylated protein clusters was found between the two groups. The tyrosine phosophorylated sites of NMⅡA were Tyr754 and Tyr1408. Correlation analysis showed that MYH9 was closely related with DDR1.
2. There was no mutation in exon 1,10,16,24-26,30-32 and 35-39 of MYH9. Western blot analysis found that the expression of NMⅡA was higher in cancer tissues than para-cancer tissues in the 28 pair tissues. In IHC analysis, NMⅡA was expressed in all cancer tissues, and were significantly higher than the expression in para-cancer tissues (100% VS 26.7%, P=0.000), strong positive expression of NMⅡA was found in 25 cancer specimen(50%) and was correlated with metastatic lymph nodes and the differentiation of the cancer but not with cancer invasive depth. Corresponding increased strong positive NMⅡA expression was correlated with the increasing metastatic lymph nodes (P=0.015<0.05) and the poorer differentiation (P=0.018<0.05). The expression of DDR1 was significantly higher in cancer tissues than para-cancer tissues (86% VS 30%, P=0.000). DDR1 expression was only correlated with the invasive depth (P=0.027<0.05), but not with metastatic lymph nodes or the differentiation of the cancer.
3. Significant differences of tyrosine phosphorylated protein levels and clusters were found between the esophageal cancer tissues and cell lines. In three cell lines, phosphorylation of the motor/contractile protein was only found in KYSE-510 cell line, and there were only three phosphorylated proteins:KLC2, MYH9 and dnnactin2. The expression of NMⅡA protein was found in all three cancer cell lines with a relative lower expression in KYSE-140 cell line.
4. The silence efficacy was highest when the ratio of SiRNA/transfection reagent was 75ng/1.5ul at 72h post-transfection with western blot analysis. MYH9 mRNA was silenced up to 89.9% demonstrated by qRT-PCR. When the expression of NMⅡA protein was almost eliminated by targeted MYH9 SiRNA, KYSE-510 cells exhibited decreased proliferation rate, planer and 3-D migration rate while with higher adhesion ability compared with cells transfected with negative SiRNA (P＜0.01).
Conclusions
1. PhosphoScan technology was successfully applicated in proteomic analysis of tyrosine phosphorylation in esophageal squamous cancer and para-cancer tissues; a number of over-expressed tyrosine phosphorylated proteins were screened in esophageal cancer tissues, of which the most obvious were the motor/contractile protein NMⅡA and the receptor tyrosine kinase DDR1;
2. Increased tyrosine phosphorylation of NMⅡA might not be induced by genetic mutation of MYH9 gene, but might be caused by elevated total NMⅡA protein expression;
3. NMⅡA expression correlated with esophageal squamous cancer differentiation and metastasis in cancer tissues; DDR1 expression only correlated with the cancer invasion depth.
4. KYSE-510 cell line expressed NMⅡA protein and tyrosine phosphorylated NMⅡA protein;
5. Decreased NMⅡA expression by targeted MYH9 SiRNA inhibited the migration and proliferation ability of KYSE-510 cell line but enhanced the adhesive ability.
方法在第一章中我们收集了28对食管鳞癌及癌旁组织标本,采用酪氨酸磷酸化抗体免疫沉淀富集酪氨酸磷酸化多肽,并用LTQ Orbitrap质谱仪进行鉴定,将鉴定结果导入Genepattern软件进行分析,筛选出差异明显的酪氨酸磷酸化蛋白质,其中酪氨酸磷酸化差异最为明显的MYH9(编码NMIIA蛋白),其与DDR1关系密切。
在第二章中我们提取了MYH9磷酸化水平最高的10例食管鳞癌组织基因组DNA,经PCR和测序检测了MYH9基因是否存在相关位点突变,western blot验证了NMⅡA蛋白在28对食管鳞癌和癌旁组织中的表达差异,采用免疫组织化学的方法研究了50例食管鳞癌组织和30例癌旁组织中NMⅡA和DDR1的表达,并与临床病理资料进行相关性分析。
在第三章中我们检测了3株食管鳞癌细胞株KYSE-140、KYSE-150、KYSE-510的酪氨酸磷酸化蛋白质谱,比较了人食管鳞癌组织和鳞癌细胞株酪氨酸磷酸化蛋白质表达的差异,同时为第四章进行NMⅡA蛋白的功能学研究提供细胞依据。
在第四章中,我们应用SiRNA沉默MYH9基因,qRT-PCR和westernblot检测SiRNA对NMⅡA蛋白的沉默水平,细胞计数明确NMⅡA蛋白沉默对细胞增殖能力的影响,细胞粘附实验检测NMⅡA蛋白沉默对细胞粘附能力的影响,划痕试验和transwell实验评价NMⅡA蛋白沉默对细胞的平面和3-D迁移能力的影响。
结果
1.在28对食管鳞癌及癌旁组织中共检测到1037种差异性酪氨酸磷酸化蛋白质,其中有477种在鳞癌组织中上调,560种在癌旁组织中上调。在肿瘤组织中酪氨酸磷酸化水平最高的是MYH9, palladin, APP, DDR1, K105种蛋白,在癌旁组织中酪氨酸磷酸化水平最高的是K23,K20, Sciellin, envoplakin, EphA15种蛋白。食管鳞癌及癌旁组织中总体酪氨酸磷酸化蛋白质无明显差异。MYH9的酪氨酸磷酸化位点是Tyr754和Tyr1408。经相关分析,MYH9与DDR1的关系密切。
2.测序结果显示MYH9基因的1,10,16,24-26,30-32,35-39等14个外显子没有检测到常见突变位点。Western blot检测表明NMⅡA蛋白在28对肿瘤组织中的表达高于癌旁组织。免疫组化显示,NMⅡA蛋白在所有的食管鳞癌组织中表达,显著高于癌旁组织(100% VS 26.7%,P=O.000),其中强阳性表达25例(50%),NMⅡA的强阳性表达与肿瘤的侵润深度无关,与淋巴结转移个数、组织学分级相关,随着转移淋巴结个数增加,NMⅡA强阳性表达率明显增加(P=0.015<0.05),低分化组病例的强阳性表达率也显著高于高分化组(P=0.018<0.05)；DDR1蛋白在肿瘤组织中阳性率显著高于癌旁组织中的阳性率(86% VS30%,P=0.000),DDR1的表达仅与肿瘤的侵润深度有关(P=0.027<0.05),与转移淋巴结个数和肿瘤组织分化程度无关。
3.食管鳞癌细胞株中的酪氨酸磷酸化蛋白质类型和磷酸化水平与鳞癌组织中的磷酸化类型和水平存在明显差异；在3株食管鳞癌细胞株中,只有KYSE-510发生了动力/收缩蛋白的酪氨酸磷酸化,并且磷酸化的动力/收缩蛋白只有KLC2, MYH9和dnnactin2三种。三株细胞株中均有NMⅡA蛋白的表达,KYSE-140的表达相对较低。
4. Western blot检测结果显示基因沉默效率在72h SiRNA/转染试剂比例为75ng/1.5ul时最高,qRT-PCR检测提示MYH9 mRNA被SiRNA沉默了89.9%,应用MYH9 SiRNA沉默KYSE-510细胞NMⅡA蛋白表达后,与阴性转染组相比,细胞的增殖速度减慢,体外粘附实验显示细胞的粘附能力增强,细胞的平面和3-D迁移能力降低(P<0.01)。
结论
1.应用PhosphoScan技术对食管鳞癌及癌旁组织进行了酪氨酸磷酸化蛋白质组学分析,筛选出了多个在食管鳞癌中酪氨酸磷酸化异常增高的蛋白质,最明显的是动力/收缩蛋白NMⅡA和受体型酪氨酸激酶DDR1；
2.食管鳞癌组织中NMⅡA的高酪氨酸磷酸化可能不是由MYH9基因突变引起,而是与组织中NMⅡA蛋白的表达量增高有关；
3.食管鳞癌组织中NMⅡA的高表达与食管鳞癌组织的分化和转移有关；DDR1蛋白的高表达只与食管鳞癌组织的侵袭性有关。
4. KYSE-510细胞表达NMⅡA蛋白和酪氨酸磷酸化NMⅡA；
5.采用SiRNA沉默MYH9基因抑制细胞内NMⅡA的表达后抑制了KYSE-510细胞的迁移和增殖能力但增强了粘附能力。
Background and purpose Esophageal cancer is the fourth most common malignancies in China and more than 90% patients are squamous cell carcinoma. Owing to the advanced stage when patients are examined, the 5-year survival rate is still low although they might receive comprehensive treatment including operation. Recently, abnormal expression of tyrosine kinase signaling pathway has been found in many tumors by some researchers, however, tyrosine phosphorylation is at low abundance in tissues. Hence there was no tyrosine phospho-proteomics research on esophageal cancer yet. Here, we investigated differential protein tyrosine phosphorylation between esophageal cancer and para-esophageal cancer normal tissues (simply, para-cancer tissues) with a new tyrosine phospho-proteomics method. This study would provide basic proof for understanding the role of tyrosine kinase signaling in the occurrence and development of esophageal cancer, and also offer new insights into the treatment and early diagnosis of esophageal cancer.
Methods In the first chapter, we collected 28 cases of esophageal squamous cancer and corresponding para-cancer tissues. Tyrosine phosphorylated peptides were enriched by immunoaffinity purification, and analyzed by LTQ Orbitrap mass spectrometer. Differential phosphorylated proteins were analyzed by using Genepattern software. MYH9 (encoding NMⅡA) was the top phosphorylated protein between the cancer and para-cancer group and was closely correlated with DDR1.
In the second chapter, we extracted genomic DNA from ten cancer tissues with highest MYH9 phosphorylation and sequenced PCR products to find any mutations of MYH9. Western blot was adopted to validate NMⅡA expression in the 28 pair specimen. Another 50 cancer specimen and 30 para-cancer normal specimen were chosen to investigate the expression of NMⅡA and DDR1 using immunohistochemistry (IHC) and correlations between their expressions and patients'clinical data were also analyzed.
In chapter three, we cultured and profiled three esophageal squamous cancer cell lines(KYSE-140、KYSE-150、KYSE-510) by mass spectrometer. Comparison of primary human esophageal cancer and cancer cell lines was made and suggested that cell lines can be used as models to validate targets identified in primary tumors.
In the fourth chapter, we silenced MYH9 with small interfering RNA; qRT-PCR and western blot were used to study the silence effect. We counted cell number to find any effect of decreased NMⅡA on cell proliferation. Cell adhesion assay was used to analyze the effect of decreased NMⅡA on cell adhesion ability. Wound closure assay and transwell assay were used to assess the effect of decreased NMⅡA on cell migration ability.
Results
1. In this study, we identified 1037 tyrosine phosphorylated proteins. 477 of them were enriched in cancers while 560 were enriched in para-cancer tissues. The top 5 tyrosine phosphorylated proteins were MYH9, palladin, APP, DDR1 and K10 in the cancer group and K23, K20, Sciellin, envoplakin and EphA1 in para-cancer group. No significant difference of tyrosine phosphorylated protein clusters was found between the two groups. The tyrosine phosophorylated sites of NMⅡA were Tyr754 and Tyr1408. Correlation analysis showed that MYH9 was closely related with DDR1.
2. There was no mutation in exon 1,10,16,24-26,30-32 and 35-39 of MYH9. Western blot analysis found that the expression of NMⅡA was higher in cancer tissues than para-cancer tissues in the 28 pair tissues. In IHC analysis, NMⅡA was expressed in all cancer tissues, and were significantly higher than the expression in para-cancer tissues (100% VS 26.7%, P=0.000), strong positive expression of NMⅡA was found in 25 cancer specimen(50%) and was correlated with metastatic lymph nodes and the differentiation of the cancer but not with cancer invasive depth. Corresponding increased strong positive NMⅡA expression was correlated with the increasing metastatic lymph nodes (P=0.015<0.05) and the poorer differentiation (P=0.018<0.05). The expression of DDR1 was significantly higher in cancer tissues than para-cancer tissues (86% VS 30%, P=0.000). DDR1 expression was only correlated with the invasive depth (P=0.027<0.05), but not with metastatic lymph nodes or the differentiation of the cancer.
3. Significant differences of tyrosine phosphorylated protein levels and clusters were found between the esophageal cancer tissues and cell lines. In three cell lines, phosphorylation of the motor/contractile protein was only found in KYSE-510 cell line, and there were only three phosphorylated proteins:KLC2, MYH9 and dnnactin2. The expression of NMⅡA protein was found in all three cancer cell lines with a relative lower expression in KYSE-140 cell line.
4. The silence efficacy was highest when the ratio of SiRNA/transfection reagent was 75ng/1.5ul at 72h post-transfection with western blot analysis. MYH9 mRNA was silenced up to 89.9% demonstrated by qRT-PCR. When the expression of NMⅡA protein was almost eliminated by targeted MYH9 SiRNA, KYSE-510 cells exhibited decreased proliferation rate, planer and 3-D migration rate while with higher adhesion ability compared with cells transfected with negative SiRNA (P＜0.01).
Conclusions
1. PhosphoScan technology was successfully applicated in proteomic analysis of tyrosine phosphorylation in esophageal squamous cancer and para-cancer tissues; a number of over-expressed tyrosine phosphorylated proteins were screened in esophageal cancer tissues, of which the most obvious were the motor/contractile protein NMⅡA and the receptor tyrosine kinase DDR1;
2. Increased tyrosine phosphorylation of NMⅡA might not be induced by genetic mutation of MYH9 gene, but might be caused by elevated total NMⅡA protein expression;
3. NMⅡA expression correlated with esophageal squamous cancer differentiation and metastasis in cancer tissues; DDR1 expression only correlated with the cancer invasion depth.
4. KYSE-510 cell line expressed NMⅡA protein and tyrosine phosphorylated NMⅡA protein;
5. Decreased NMⅡA expression by targeted MYH9 SiRNA inhibited the migration and proliferation ability of KYSE-510 cell line but enhanced the adhesive ability.
引文
[1]Parkin DM, Bray F, Ferlay J, et al. Global Cancer Statistics,2002. CA Cancer J Clin.2005,55(2):74-108.
[2]中华人民共和国卫生部《2009中国卫生统计年鉴》,2009：254.
[3]Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med.2003, 349(23):2241-52.
[4]Fumoto S, Shimokuni T, Tanimoto K, et al. Selection of a novel drug-response predictor in esophageal cancer:A novel screening method using microarray and identification of IFITM1 as a potent marker gene of CDDP response. Int J Oncol.2008,32(2):413-23.
[5]Vogelstein B., Kinzler K.W. Cancer genes and the pathways they control. Nat Med 2004,10:789-99.
[6]Grimsrud PA, Swaney DL, Wenger CD, et al. Phosphoproteomics for the masses. ACS Chem Biol.2010,5(1):105-19.
[7]Johnson SA, Hunter T. Kinomics:methods for deciphering the kinome. Nat Meth.2005,2(1):17-25.
[8]Manning G, Whyte DB, Martinez R, et al. The protein kinase complement of the human genome. Science.2002,298(5600):1912-34.
[9]Michael Deininger, Tyrosine Kinase Inhibitors[A] Gewirtz DA., Holt S.E., Grant S. Cancer Drμg Discovery and Development Apoptosis, Senescence, and Cancer[M]. Humana Press,2007,477-508.
[10]Mayya V, Han DK. Phosphoproteomics by mass spectrometry:insights, implications, applications and limitations. Expert Rev Proteomics.2009,6(6):605-18.
[11]Hunter T. Signaling-2000 and beyond. Cell.2000,100(1):113-27.
[12]Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell.2000,103(2):211-25.
[13]Hunter T. Tyrosine phosphorylation:thirty years and counting. Curr Opin Cell Biol.2009,21(2):140-6.
[14]Pande AU, Iyer RV, Rani A, et al. Epidermal growth factor receptor-directed therapy in esophageal cancer. Oncology-basel.2007,73(5-6):281-9.
[15]Hara F, Aoe M, Doihara H, et al. Antitumor effect of gefitinib ('Iressa') on esophageal squamous cell carcinoma cell lines in vitro and in vivo. Cancer Lett.2005,226(1):37-47.
[16]Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA, et al. Predictive factors for outcome in a phase Ⅱ study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol.2006,24(10):1612-9.
[17]Guo M, Liu S, Herman JG, et al. Gefitinib-sensitizing mutation in esophageal carcinoma cell line Kyse450. Cancer Biol Ther.2006,5(2):152-5.
[18]Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell.2007,131(6):1190-203.
[19]Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature.2007,448(7153):561-6.
[20]Meyerson M. Cancer:broken genes in solid tumours. Nature.2007,448(7153):545-6.
[21]Chong PK, Lee H, Kong JW, et al. Phosphoproteomics, oncogenic signaling and cancer research. Proteomics.2008,8(21):4370-82.
[22]Pawson T, Scott JD. Protein phosphorylation in signaling-50 years and counting. Trends Biochem Sci.2005,30(6):286-90.
[23]Moran MF, Tong J, Taylor P, et al. Emerging applications for phospho-proteomics in cancer molecular therapeutics. Biochim Biophys Acta.2006,1766(2):230-41.
[24]Ashman K, Villar EL. Phosphoproteomics and cancer research. Clin Transl Oncol.2009,11(6):356-62.
[25]Paradela A, Albar JP. Advances in the analysis of protein phosphorylation. J Proteome Res.2008,7 (5):1809-18.
[26]Olsen JV, Vermeulen M, Santamaria A, et al. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal.2010,3(104):ra3.
[27]Schreiber TB, Mausbacher N, Breitkopf SB, et al. Quantitative phosphoproteomics-an emerging key technology in signal-transduction research. Proteomics.2008,8(21):4416-32.
[28]Preisinger C, von Kriegsheim A, Matallanas D, et al. Proteomics and phosphoproteomics for the mapping of cellular signalling networks. Proteomics.2008,8(21):4402-15.
[29]Leroy C, Fialin C, Sirvent A, et al. Quantitative phosphoproteomics reveals a cluster of tyrosine kinases that mediates SRC invasive activity in advanced colon carcinoma cells. Cancer Res.2009,69(6):2279-86.
[30]Beausoleil SA, Jedrychowski M, Schwartz D, et al. Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A.2004,101(33):12130-5.
[31]Ficarro S, Chertihin O, Westbrook VA, et al. Phosphoproteome analysis of capacitated human sperm. Evidence of tyrosine phosphorylation of a kinase-anchoring protein 3 and valosin-containing protein/p97 during capacitation. J Biol Chem.2003,278(13):11579-89.
[32]Simons M, Wang M, McBride OW, et al. Human nonmuscle myosin heavy chains are encoded by two genes located on different chromosomes. Circ Res.1991,69(2):530-9.
[33]Toothaker L, Gonzalez D, Tung N, et al. Cellular myosin heavy chain in human leukocytes:isolation of 5'cDNA clones, characterization of the protein, chromosomal localization, and upregulation during myeloid differentiation. Blood.1991,78(7):1826-33.
[34]Vicente-Manzanares M, Ma X, Adelstein RS, et al. Non-muscle myosin Ⅱ takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol.2009,10(11):778-90.
[35]Conti MA, Even-Ram S, Liu C, et al. Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain Ⅱ-A in mice. J Biol Chem.2004,279(40):41263-6.
[36]Kelley MJ, Jawien W, Ortel TL, et al. Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly. Nat Genet.2000,26(1):106-8.
[37]Seri M, Cusano R, Gangarossa S, et al. Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium. Nat Genet.2000,26(1):103-5.
[38]Kunishima S, Kojima T, Matsushita T, et al. Mutations in the NMMHC-A gene cause autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly/Sebastian syndrome). Blood.2001,97(4):1147-9.
[39]Ozsahinog, lu C, Kumi M, et al. Hereditary macrothrombocytopathia, deafness and nephritis (Epstein's triad). Int J Pediatr Otorhi.1985,9(3):257-61.
[40]Peterson L, Rao K, Crosson J, et al. Fechtner syndrome-a variant of Alport's syndrome with leukocyte inclusions and macrothrombocytopenia. Blood.1985,65(2):397-406.
[41]Greinacher A, Nieuwenhuis HK, White JG. Sebastian platelet syndrome:A new variant of hereditary macrothrombocytopenia with leukocyte inclusions. Ann Hematol.1990,61(5):282-8.
[42]Ludowyke RI, Elgundi Z, Kranenburg T, et al. Phosphorylation of nonmuscle myosin heavy chain ⅡA on Ser1917 is mediated by protein kinase C beta Ⅱ and coincides with the onset of stimulated degranulation of RBL-2H3 mast cells. J Immunol.2006,177(3):1492-9.
[43]Murakami N, Chauhan VP, Elzinga M. Two nonmuscle myosin Ⅱ heavy chain isoforms expressed in rabbit brains:filament forming properties, the effects of phosphorylation by protein kinase C and casein kinase Ⅱ, and location of the phosphorylation sites. Biochemistry-us.1998,37(7):1989-2003.
[44]Clark K, Middelbeek J, Dorovkov MV, et al. The alpha-kinases TRPM6 and TRPM7, but not eEF-2 kinase, phosphorylate the assembly domain of myosin ⅡA, ⅡB and ⅡC. Febs Lett.2008,582(20):2993-7.
[45]Clark K, Middelbeek J, Lasonder E, et al. TRPM7 regulates myosin ⅡA filament stability and protein localization by heavy chain phosphorylation. J Mol Biol.2008,378(4):790-803.
[46]Minamiya Y, Nakagawa T, Saito H, et al. Increased expression of myosin light chain kinase mRNA is related to metastasis in non-small cell lung cancer. Tumour Biol.2005,26(3):153-7.
[47]Barkan D, Kleinman H, Simmons JL, et al. Inhibition of Metastatic Outgrowth from Single Dormant Tumor Cells by Targeting the Cytoskeleton. Cancer Res.2008,68(15):6241-50.
[48]Dulyaninova NG, House RP, Betapudi V, et al. Myosin-IIA heavy-chain phosphorylation regulates the motility of MDA-MB-231 carcinoma cells. Mol Biol Cell.2007,18(8):3144-55.
[49]Dulyaninova NG, Malashkevich VN, Almo SC, et al. Regulation of myosin-IIA assembly and Mtsl binding by heavy chain phosphorylation. Biochemistry-us.2005,44(18):6867-76.
[50]Li ZH, Spektor A, Varlamova O, et al. Mts1 regulates the assembly of nonmuscle myosin-ⅡA. Biochemistry-us.2003,42(48):14258-66.
[51]Ismail TM, Fernig DG, Rudland PS, et al. The basic C-terminal amino acids of calcium-binding protein S100A4 promote metastasis. Carcinogenesis.2008,29(12):2259-66.
[52]Johnson JD, Edman JC, Rutter WJ. A receptor tyrosine kinase found in breast carcinoma cells has an extracellular discoidin I-like domain. Proc Natl Acad Sci U S A.1993,90(12):5677-81.
[53]Abdulhussein R, Koo DH, Vogel WF. Identification of disulfide-linked dimers of the receptor tyrosine kinase DDR1. J Biol Chem.2008,283(18):12026-33.
[54]Yoshimura T, Matsuyama W, Kamohara H. Discoidin domain receptor 1:a new class of receptor regulating leukocyte-collagen interaction. Immunol Res.2005,31(3):219-30.
[55]Vogel WF, Abdulhussein R, Ford CE. Sensing extracellular matrix:an update on discoidin domain receptor function. Cell Signal.2006,18(8):1108-16.
[56]Wang CZ, Yeh YC, Tang MJ. DDR1/E-cadherin complex regulates the activation of DDR1 and cell spreading. Am J Physiol Cell Physiol.2009,297(2):C419-29.
[57]Yoshida D, Teramoto A. Enhancement of pituitary adenoma cell invasion and adhesion is mediated by discoidin domain receptor-1. J Neurooncol.2007,82(1):29-40.
[58]Nemoto T, Ohashi K, Akashi T, et al. Overexpression of protein tyrosine kinases in human esophageal cancer. Pathobiology.1997,65(4):195-203.
[59]李超,向小勇,陈力,等.DDR1蛋白在食管鳞癌组织中的表达及临床意义.内分泌外科杂志.2007,1(4)：252-4.
[60]Davies H, Hunter C, Smith R, et al. Somatic Mutations of the Protein Kinase Gene Family in Human Lung Cancer. Cancer Res.2005,65(17):7591-5.
[61]Ford CE, Lau SK, Zhu CQ, et al. Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma. Br J Cancer.2007,96(5):808-14.
[62]Huang Y, Arora P, McCulloch CA, et al. The collagen receptor DDR1 regulates cell spreading and motility by associating with myosin ⅡA. J Cell Sci.2009,122(Pt 10):1637-46.
[63]Faraci-Orf E, McFadden C, Vogel WF. DDR1 signaling is essential to sustain Stat5 function during lactogenesis. J Cell Biochem.2006,97(1):109-21.
[64]Seri M, Pecci A, Di Bari F, et al. MYH9-related disease:May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore).2003,82(3):203-15.
[65]Kunishima S, Matsushita T, Kojima T, et al. Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions. J Hum Genet.2001,46(12):722-9.
[66]Maeda J, Hirano T, Ogiwara A, et al. Proteomic analysis of stage I primary lung adenocarcinoma aimed at individualisation of postoperative therapy. Br J Cancer.2008,98(3):596-603.
[67]Dong F, Li S, Pujol-Moix N, et al. Genotype-phenotype correlation in MYH9-related thrombocytopenia. Br J Haematol.2005,130(4):620-7.
[68]Kunishima S, Matsushita T, Yoshihara T, et al. First description of somatic mosaicism in MYH9 disorders. Br J Haematol.2005,128(3):360-5.
[69]Kunishima S, Takaki K, Ito Y, et al. Germinal mosaicism in MYH9 disorders:a family with two affected siblings of normal parents. Br J Haematol.2009,145(2):260-2.
[70]Jia ZL, Li Y, Chen CH, et al. Association among polymorphisms at MYH9, environmental factors, and nonsyndromic orofacial clefts in western China. Dna Cell Biol.2010,29(1):25-32.
[71]Nunez M, Saran AM, Freedman BI. Gene-gene and gene-environment interactions in HIV-associated nephropathy:A focus on the MYH9 nephropathy susceptibility gene. Adv Chronic Kidney Dis.2010,17(1):44-51.
[72]Sekine T, Konno M, Sasaki S, et al. Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease. Kidney Int.2010.
[73]Winkler CA, Nelson G, Oleksyk TK, et al. Genetics of focal segmental glomerulosclerosis and human immunodeficiency virus-associated collapsing glomerulopathy:the role of MYH9 genetic variation. Semin Nephrol.2010,30(2):111-25.
[74]Cai Y, Biais N, Giannone G, et al. Nonmuscle myosin ⅡA-dependent force inhibits cell spreading and drives F-actin flow. Biophys J.2006,91(10):3907-20.
[75]Betapudi V, Licate LS, Egelhoff TT. Distinct roles of nonmuscle myosin Ⅱ isoforms in the regulation of MDA-MB-231 breast cancer cell spreading and migration. Cancer Res.2006,66(9):4725-33.
[76]Duxbury MS, Ashley SW, Whang EE. Inhibition of pancreatic adenocarcinoma cellular invasiveness by blebbistatin:a novel myosin Ⅱ inhibitor. Biochem Biophys Res Commun.2004,313(4):992-7.
[77]Wei Q, Adelstein RS. Conditional expression of a truncated fragment of nonmuscle myosin Ⅱ-A alters cell shape but not cytokinesis in HeLa cells. Mol Biol Cell.2000,11(10):3617-27.
[78]Bao J, Jana SS, Adelstein RS. Vertebrate nonmuscle myosin Ⅱ isoforms rescue small interfering RNA-induced defects in COS-7 cell cytokinesis. J Biol Chem.2005,280(20):19594-9.
[79]Babbin BA, Koch S, Bachar M, et al. Non-muscle myosin ⅡA differentially regulates intestinal epithelial cell restitution and matrix invasion. Am J Pathol.2009,174(2):436-48.
[80]Tarabykina S, Griffiths TR, Tulchinsky E, et al. Metastasis-associated protein S100A4:spotlight on its role in cell migration. Curr Cancer Drμg Targets.2007,7(3):217-28.
[81]Wang HY, Zhang JY, Cui JT, et al. Expression status of S100A14 and S100A4 correlates with metastatic potential and clinical outcome in colorectal cancer after surgery. Oncol Rep.2010,23(1):45-52.
[82]Wang YY, Ye ZY, Zhao ZS, et al. High-level expression of S100A4 correlates with lymph node metastasis and poor prognosis in patients with gastric cancer. Ann Surg Oncol.2010,17(1):89-97.
[83]Tabata T, Tsukamoto N, Fooladi AA, et al. RNA interference targeting against S100A4 suppresses cell growth and motility and induces apoptosis in human pancreatic cancer cells. Biochem Biophys Res Commun.2009,390(3):475-80.
[84]Ismail NI, Kaur G, Hashim H, et al. S100A4 overexpression proves to be independent marker for breast cancer progression. Cancer Cell Int.2008,8:12.
[85]Ninomiya I, Ohta T, Fushida S, et al. Increased expression of S100A4 and its prognostic significance in esophageal squamous cell carcinoma. Int J Oncol.2001,18(4):715-20.
[86]Tsuna M, Kageyama S, Fukuoka J, et al. Significance of S100A4 as a prognostic marker of lung squamous cell carcinoma. Anticancer Res.2009,29(7):2547-54.
[87]Donato R. Intracellular and extracellular roles of S100 proteins. Microsc Res Tech.2003,60(6):540-51.
[88]Kim EJ, Helfman DM. Characterization of the metastasis-associated protein, S100A4. Roles of calcium binding and dimerization in cellular localization and interaction with myosin. J Biol Chem.2003,278(32):30063-73.
[89]Li ZH, Bresnick AR. The S100A4 metastasis factor regulates cellular motility via a direct interaction with myosin-IIA. Cancer Res.2006,66(10):5173-80.
[90]Santamaria-Kisiel L, Rintala-Dempsey AC, Shaw GS. Calcium-dependent and-independent interactions of the S100 protein family. Biochem J.2006,396(2):201-14.
[91]Hua J, Chen D, Fu H, et al. Short hairpin RNA-mediated inhibition of S100A4 promotes apoptosis and suppresses proliferation of BGC823 gastric cancer cells in vitro and in vivo. Cancer Lett.2009.
[92]Heinzelmann-Schwarz VA, Gardiner-Garden M, Henshall SM, et al. Overexpression of the cell adhesion molecules DDR1, Claudin 3, and Ep-CAM in metaplastic ovarian epithelium and ovarian cancer. Clin Cancer Res.2004,10(13):4427-36.
[93]Shimada K, Nakamura M, Ishida E, et al. Prostate cancer antigen-1 contributes to cell survival and invasion thoμgh discoidin receptor 1 in human prostate cancer. Cancer Sci.2008,99(1):39-45.
[94]Weiner HL, Huang H, Zagzag D, et al. Consistent and selective expression of the discoidin domain receptor-1 tyrosine kinase in human brain tumors. Neurosurgery.2000,47(6):1400-9.
[95]Yamanaka R, Arao T, Yajima N, et al. Identification of expressed genes characterizing long-term survival in malignant glioma patients. Oncogene.2006,25(44):5994-6002.
[96]Das S, Ongusaha PP, Yang YS, et al. Discoidin domain receptor 1 receptor tyrosine kinase induces cyclooxygenase-2 and promotes chemoresistance throμgh nuclear factor-kappaB pathway activation. Cancer Res.2006,66(16):8123-30.
[97]Bantscheff M, Eberhard D, Abraham Y, et al. Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat Biotechnol.2007,25(9):1035-44.
[98]Rix U, Hantschel O, Durnberger G, et al. Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood.2007,110(12):4055-63.
[99]Day E, Waters B, Spiegel K, et al. Inhibition of collagen-induced discoidin domain receptor 1 and 2 activation by imatinib, nilotinib and dasatinib. Eur J Pharmacol.2008,599(1-3):44-53.
[100]Conti MA, Adelstein RS. Nonmuscle myosin Ⅱ moves in new directions. J Cell Sci.2008,121(Pt1):11-8.
[101]Poincloux R, Lizarraga F, Chavrier P. Matrix invasion by tumour cells:a focus on MT1-MMP trafficking to invadopodia. J Cell Sci.2009,122(Pt 17):3015-24.
[102]Golomb E, Ma X, Jana SS, et al. Identification and characterization of nonmuscle myosin II-C, a new member of the myosin Ⅱ family. J Biol Chem.2004,279(4):2800-8.
[103]Swailes NT, Colegrave M, Knight PJ, et al. Non-muscle myosins 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse. J Cell Sci.2006,119(Pt 17):3561-70.
[104]Yuen SL, Ogut O, Brozovich FV. Nonmuscle myosin is regulated during smooth muscle contraction. Am J Physiol Heart Circ Physiol.2009,297(1):H191-9.
[105]Morano I, Chai G-X, Baltas LG, et al. Smooth-muscle contraction without smooth-muscle myosin. Nat Cell Biol.2000,2(6):371-5.
[106]Edwards RA. Laser capture microdissection of mammalian tissue. J Vis Exp.2007(8):309.
[107]Mustafa D, Kros JM, Luider T. Combining laser capture microdissection and proteomics techniques. Methods Mol Biol.2008,428:159-78.
[108]Liu Y, Wu J, Yan G, et al. Proteomic analysis of prolactinoma cells by immuno-laser capture microdissection combined with online two-dimensional nano-scale liquid chromatography/mass spectrometry. Proteome Sci.2010,8:2.
[109]Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature.1998,391 (6669):806-11.
[110]Kaiser JP, Reinmann A, Bruinink A. The effect of topographic characteristics on cell migration velocity. Biomaterials.2006,27(30):5230-41.
[111]Gupton SL, Waterman-Storer CM. Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration. Cell.2006,125(7):1361-74.
[112]Rhee S. Fibroblasts in three dimensional matrices:cell migration and matrix remodeling. Exp Mol Med.2009,41(12):858-65.
[113]Green JA, Yamada KM. Three-dimensional microenvironments modulate fibroblast signaling responses. Adv Drug Deliv Rev.2007,59(13):1293-8.
[114]Li Y, Friedmann DR, Mhatre AN, et al. MYH9-siRNA and MYH9 mutant alleles:expression in cultured cell lines and their effects upon cell structure and function. Cell Motil Cytoskeleton.2008,65(5):393-405.
[115]Jana SS, Kawamoto S, Adelstein RS. A specific isoform of nonmuscle myosin II-C is required for cytokinesis in a tumor cell line. J Biol Chem.2006,281(34):24662-70.
[116]Beadle C, Assanah MC, Monzo P, et al. The role of myosin II in glioma invasion of the brain. Mol Biol Cell.2008,19(8):3357-68.
[117]Limouze J, Straight AF, Mitchison T, et al. Specificity of blebbistatin, an inhibitor of myosin Ⅱ. J Muscle Res Cell Motil.2004,25(4-5):337-41.
[118]Vicente-Manzanares M, Koach MA, Whitmore L, et al. Segregation and activation of myosin ⅡB creates a rear in migrating cells. J Cell Biol.2008,183(3):543-54.
[119]Zaidel-Bar R, Ballestrem C, Kam Z, et al. Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells. J Cell Sci.2003,116(Pt22):4605-13.
[120]Yamazaki D, Kurisu S, Takenawa T. Regulation of cancer cell motility through actin reorganization. Cancer Sci.2005,96(7):379-86.
[121]Lauffenburger DA, Horwitz AF. Cell migration:a physically integrated molecular process. Cell.1996,84(3):359-69.
[122]Vicente-Manzanares M, Zareno J, Whitmore L, et al. Regulation of protrusion, adhesion dynamics, and polarity by myosins ⅡA and ⅡB in migrating cells. J Cell Biol.2007,176(5):573-80.
[123]Sandquist JC, Swenson KI, DeMali KA, et al. Rho Kinase Differentially Regulates Phosphorylation of Nonmuscle Myosin Ⅱ Isoforms A and B during Cell Rounding and Migration. J Biol Chem.2006,281(47):35873-83.
[124]Even-Ram S, Doyle AD, Conti MA, et al. Myosin ⅡA regulates cell motility and actomyosin-microtubule crosstalk. Nat Cell Biol.2007,9(3):299-309.
[1]Odronitz F, Kollmar M. Drawing the tree of eukaryotic life based on the analysis of 2,269 manually annotated myosins from 328 species. Genome Biol.2007,8(9):R196.
[2]Sellers JR. Myosins:a diverse superfamily. Biochim Biophys Acta.2000,1496(1):3-22.
[3]Golomb E, Ma X, Jana SS, et al. Identification and characterization of nonmuscle myosin Ⅱ-C, a new member of the myosin Ⅱ family. J Biol Chem.2004,279(4):2800-8.
[4]Swailes NT, Colegrave M, Knight PJ, et al. Non-muscle myosins 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse. J Cell Sci.2006,119(Pt 17):3561-70.
[5]Yuen SL, Ogut O, Brozovich FV. Nonmuscle myosin is regulated during smooth muscle contraction. Am J Physiol Heart Circ Physiol.2009,297(1):H191-9.
[6]Morano I, Chai G-X, Baltas LG, et al. Smooth-muscle contraction without smooth-muscle myosin. Nat Cell Biol.2000,2(6):371-5.
[7]Uren D, Hwang HK, Hara Y, et al. Gene dosage affects the cardiac and brain phenotype in nonmuscle myosin Ⅱ-B-depleted mice. J Clin Invest.2000,105(5):663-71.
[8]Simons M, Wang M, McBride OW, et al. Human nonmuscle myosin heavy chains are encoded by two genes located on different chromosomes. Circ Res.1991,69(2):530-9.
[9]Toothaker L, Gonzalez D, Tung N, et al. Cellular myosin heavy chain in human leukocytes:isolation of 5' cDNA clones, characterization of the protein, chromosomal localization, and upregulation during myeloid differentiation. Blood.1991,78(7):1826-33.
[10]Maupin P, Phillips CL, Adelstein RS, et al. Differential localization of myosin-Ⅱ isozymes in human cultured cells and blood cells. J Cell Sci.1994,107 (Pt 11):3077-90.
[11]Rochlin MW, Itoh K, Adelstein RS, et al. Localization of myosin Ⅱ A and B isoforms in cultured neurons. J Cell Sci.1995,108 (Pt 12):3661-70.
[12]Straussman R, Ben-Ya'acov A, Woolfson DN, et al. Kinking the coiled coil-negatively charged residues at the coiled-coil interface. J Mol Biol.2007,366(4):1232-42.
[13]Svitkina TM, Verkhovsky AB, Borisy GG. Improved procedures for electron microscopic visualization of the cytoskeleton of cultured cells. J Struct Biol.1995,115(3):290-303.
[14]Scholey JM, Taylor KA, Kendrick-Jones J. Regulation of non-muscle myosin assembly by calmodulin-dependent light chain kinase. Nature.1980,287(5779):233-5.
[15]Vicente-Manzanares M, Koach MA, Whitmore L, et al. Segregation and activation of myosin ⅡB creates a rear in migrating cells. J Cell Biol.2008,183(3):543-54.
[16]Jung HS, Komatsu S, Ikebe M, et al. Head-head and head-tail interaction:a general mechanism for switching off myosin Ⅱ activity in cells. Mol Biol Cell.2008,19(8):3234-42.
[17]Craig R, Woodhead JL. Structure and function of myosin filaments. Curr Opin Struct Biol.2006,16(2):204-12.
[18]Vicente-Manzanares M, Ma X, Adelstein RS, et al. Non-muscle myosin Ⅱ takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol.2009,10(11):778-90.
[19]Kim KY, Kovacs M, Kawamoto S, et al. Disease-associated mutations and alternative splicing alter the enzymatic and motile activity of nonmuscle myosins Ⅱ-B and Ⅱ-C. J Biol Chem.2005,280(24):22769-75.
[20]Bao J, Ma X, Liu C, et al. Replacement of nonmuscle myosin Ⅱ-B with Ⅱ-A rescues brain but not cardiac defects in mice. J Biol Chem.2007,282(30):22102-11.
[21]Nakasawa T, Takahashi M, Matsuzawa F, et al. Critical regions for assembly of vertebrate nonmuscle myosin Ⅱ. Biochemistry-us.2005,44(1):174-83.
[22]Sandquist JC, Means AR. The C-terminal tail region of nonmuscle myosin Ⅱ directs isoform-specific distribution in migrating cells. Mol Biol Cell.2008,19(12):5156-67.
[23]Ikebe M. Phosphorylation of a second site for myosin light chain kinase on platelet myosin. Biochemistry-us.1989,28(22):8750-5.
[24]Somlyo AP, Somlyo AV. Ca2+sensitivity of smooth muscle and nonmuscle myosin Ⅱ:modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev.2003,83(4):1325-58.
[25]Hirata N, Takahashi M, Yazawa M. Diphosphorylation of regulatory light chain of myosin ⅡA is responsible for proper cell spreading. Biochem Biophys Res Commun.2009,381(4):682-7.
[26]Matsumura F. Regulation of myosin Ⅱ during cytokinesis in higher eukaryotes. Trends Cell Biol.2005,15(7):371-7.
[27]Zhao ZS, Manser E. PAK and other Rho-associated kinases-effectors with surprisingly diverse mechanisms of regulation. Biochem J.2005,386(Pt 2):201-14.
[28]Kimura K, Ito M, Amano M, et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science.1996,273(5272):245-8.
[29]Sandquist JC, Swenson KI, DeMali KA, et al. Rho Kinase Differentially Regulates Phosphorylation of Nonmuscle Myosin Ⅱ Isoforms A and B during Cell Rounding and Migration. J Biol Chem.2006,281(47):35873-83.
[30]Totsukawa G, Yamakita Y, Yamashiro S, et al. Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts. J Cell Biol.2000,150(4):797-806.
[31]Totsukawa G, Wu Y, Sasaki Y, et al. Distinct roles of MLCK and ROCK in the regulation of membrane protrusions and focal adhesion dynamics during cell migration of fibroblasts. J Cell Biol.2004,164(3):427-39.
[32]Burridge K, Wennerberg K. Rho and Rac take center stage. Cell.2004,116(2):167-79.
[33]Garcia-Mata R, Burridge K. Catching a GEF by its tail. Trends Cell Biol.2007,17(1):36-43.
[34]IKebe M, Reardon S. Phosphorylation of bovine platelet myosin by protein kinase C. Biochemistry-us.1990,29(11):2713-20.
[35]Komatsu S, IKebe M. The phosphorylation of myosin Ⅱ at the Ser1 and Ser2 is critical for normal platelet-derived growth factor induced reorganization of myosin filaments. Mol Biol Cell.2007,18(12):5081-90.
[36]Ludowyke RI, Elgundi Z, Kranenburg T, et al. Phosphorylation of nonmuscle myosin heavy chain ⅡA on Ser1917 is mediated by protein kinase C beta Ⅱ and coincides with the onset of stimulated degranulation of RBL-2H3 mast cells. J Immunol.2006,177(3):1492-9.
[37]Murakami N, Chauhan VP, Elzinga M. Two nonmuscle myosin Ⅱ heavy chain isoforms expressed in rabbit brains:filament forming properties, the effects of phosphorylation by protein kinase C and casein kinase Ⅱ, and location of the phosphorylation sites. Biochemistry-us.1998,37(7):1989-2003.
[38]Dulyaninova NG, Malashkevich VN, Almo SC, et al. Regulation of myosin-ⅡA assembly and Mtsl binding by heavy chain phosphorylation. Biochemistry-us.2005,44(18):6867-76.
[39]Li ZH, Spektor A, Varlamova O, et al. Mts1 regulates the assembly of nonmuscle myosin-Ⅱ A. Biochemistry-us.2003,42(48):14258-66.
[40]Li ZH, Bresnick AR. The S100A4 metastasis factor regulates cellular motility via a direct interaction with myosin-Ⅱ A. Cancer Res.2006,66(10):5173-80.
[41]Clark K, Middelbeek J, Dorovkov MV, et al. The alpha-kinases TRPM6 and TRPM7, but not eEF-2 kinase, phosphorylate the assembly domain of myosin Ⅱ A, ⅡB and ⅡC. Febs Lett.2008,582(20):2993-7.
[42]Clark K, Middelbeek J, Lasonder E, et al. TRPM7 regulates myosin ⅡA filament stability and protein localization by heavy chain phosphorylation. J Mol Biol.2008,378(4):790-803.
[43]Mseka T, Bamburg JR, Cramer LP. ADF/cofilin family proteins control formation of oriented actin-filament bundles in the cell body to trigger fibroblast polarization. J Cell Sci.2007,120(Pt 24):4332-44.
[44]Yam PT, Wilson CA, Ji L, et al. Actin-myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility. J Cell Biol.2007,178(7):1207-21.
[45]Vicente-Manzanares M, Zareno J, Whitmore L, et al. Regulation of protrusion, adhesion dynamics, and polarity by myosins ⅡA and ⅡB in migrating cells. J Cell Biol.2007,176(5):573-80.
[46]Cai Y, Biais N, Giannone G, et al. Nonmuscle myosin Ⅱ A-dependent force inhibits cell spreading and drives F-actin flow. Biophys J.2006,91(10):3907-20.
[47]Even-Ram S, Doyle AD, Conti MA, et al. Myosin ⅡA regulates cell motility and actomyosin-microtubule crosstalk. Nat Cell Biol.2007,9(3):299-309.
[48]Lauffenburger DA, Horwitz AF. Cell migration:a physically integrated molecular process. Cell.1996,84(3):359-69.
[49]Ridley AJ, Schwartz MA, Burridge K, et al. Cell migration:integrating signals from front to back. Science.2003,302(5651):1704-9.
[50]Small JV, Resch GP. The comings and goings of actin:coupling protrusion and retraction in cell motility. Curr Opin Cell Biol.2005,17(5):517-23.
[51]Kaverina I, Krylyshkina O, Small JV. Regulation of substrate adhesion dynamics during cell motility. Int J Biochem Cell Biol.2002,34(7):746-61.
[52]Gupton SL, Waterman-Storer CM. Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration. Cell.2006,125(7):1361-74.
[53]Webb DJ, Donais K, Whitmore LA, et al. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol.2004,6(2):154-61.
[54]Giannone G, Dubin-Thaler BJ, Rossier O, et al. Lamellipodial actin mechanically links myosin activity with adhesion-site formation. Cell.2007,128(3):561-75.
[55]Betapudi V, Licate LS, Egelhoff TT. Distinct roles of nonmuscle myosin Ⅱ isoforms in the regulation of MDA-MB-231 breast cancer cell spreading and migration. Cancer Res.2006,66(9):4725-33.
[56]Beadle C, Assanah MC, Monzo P, et al. The role of myosin Ⅱ in glioma invasion of the brain. Mol Biol Cell.2008,19(8):3357-68.
[57]Babbin BA, Koch S, Bachar M, et al. Non-muscle myosin ⅡA differentially regulates intestinal epithelial cell restitution and matrix invasion. Am J Pathol.2009,174(2):436-48.
[58]Conti MA, Even-Ram S, Liu C, et al. Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain Ⅱ-A in mice. J Biol Chem.2004,279(40):41263-6.
[59]Ivanov AI, McCall IC, Parkos CA, et al. Role for actin filament turnover and a myosin Ⅱ motor in cytoskeleton-driven disassembly of the epithelial apical junctional complex. Mol Biol Cell.2004,15(6):2639-51.
[60]Ivanov AI, Bachar M, Babbin BA, et al. A unique role for nonmuscle myosin heavy chain ⅡA in regulation of epithelial apical junctions. PLoS One.2007,2(7):e658.
[61]Shewan AM, Maddugoda M, Kraemer A, et al. Myosin 2 is a key Rho kinase target necessary for the local concentration of E-cadherin at cell-cell contacts. Mol Biol Cell.2005,16(10):4531-42.
[62]Yamada S, Nelson WJ. Localized zones of Rho and Rac activities drive initiation and expansion of epithelial cell-cell adhesion. J Cell Biol.2007,178(3):517-27.
[63]Carmona-Fontaine C, Matthews HK, Kuriyama S, et al. Contact inhibition of locomotion in vivo controls neural crest directional migration. Nature.2008,456(7224):957-61.
[64]Kelley MJ, Jawien W, Ortel TL, et al. Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly. Nat Genet.2000,26(1):106-8.
[65]Seri M, Cusano R, Gangarossa S, et al. Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium. Nat Genet.2000,26(1):103-5.
[66]Kunishima S, Kojima T, Matsushita T, et al. Mutations in the NMMHC-A gene cause autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly/Sebastian syndrome). Blood.2001,97(4):1147-9.
[67]Ozsahinog, lu C, Kiimi M, et al. Hereditary macrothrombocytopathia, deafness and nephritis (Epstein's triad). Int J Pediatr Otorhi.1985,9(3):257-61.
[68]Peterson L, Rao K, Crosson J, et al. Fechtner syndrome-a variant of Alport's syndrome with leukocyte inclusions and macrothrombocytopenia. Blood.1985,65(2):397-406.
[69]Greinacher A, Nieuwenhuis HK, White JG. Sebastian platelet syndrome:A new variant of hereditary macrothrombocytopenia with leukocyte inclusions. Ann Hematol.1990,61(5):282-8.
[70]Seri M, Pecci A, Di Bari F, et al. MYH9-related disease:May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore).2003,82(3):203-15.
[71]Dong F, Li S, Pujol-Moix N, et al. Genotype-phenotype correlation in MYH9-related thrombocytopenia. Br J Haematol.2005,130(4):620-7.
[72]Sekine T, Konno M, Sasaki S, et al. Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease. Kidney Int.2010.
[73]Pecci A, Panza E, Pujol-Moix N, et al. Position of nonmuscle myosin heavy chain ⅡA (NMMHC-ⅡA) mutations predicts the natural history of MYH9-related disease. Hum Mutat.2008,29(3):409-17.
[74]Kunishima S, Matsushita T, Yoshihara T, et al. First description of somatic mosaicism in MYH9 disorders. Br J Haematol.2005,128(3):360-5.
[75]Kunishima S, Takaki K, Ito Y, et al. Germinal mosaicism in MYH9 disorders:a family with two affected siblings of normal parents. Br J Haematol.2009,145(2):260-2.
[76]Burt RA, Joseph JE, Milliken S, et al. Description of a novel mutation leading to MYH9-related disease. Thromb Res.2008,122(6):861-3.
[77]de Rocco D, Heller PG, Girotto G, et al. MYH9 related disease:a novel missense Ala95Asp mutation of the MYH9 gene. Platelets.2009,20(8):598-602.
[78]Pecci A, Panza E, De Rocco D, et al. MYH9 related disease:four novel mutations of the tail domain of myosin-9 correlating with a mild clinical phenotype. Eur J Haematol.2009.
[79]Marigo V, Nigro A, Pecci A, et al. Correlation between the clinical phenotype of MYH9-related disease and tissue distribution of class Ⅱ nonmuscle myosin heavy chains. Genomics.2004,83(6):1125-33.
[80]Kunishima S, Hamaguchi M, Saito H. Differential expression of wild-type and mutant NMMHC-ⅡA polypeptides in blood cells suggests cell-specific regulation mechanisms in MYH9 disorders. Blood.2008,111(6):3015-23.
[81]Canobbio I, Noris P, Pecci A, et al. Altered cytoskeleton organization in platelets from patients with MYH9-related disease. J Thromb Haemost.2005,3(5):1026-35.
[82]Di Pumpo M, Noris P, Pecci A, et al. Defective expression of GPIb/IX/V complex in platelets from patients with May-Hegglin anomaly and Sebastian syndrome. Haematologica.2002,87(9):943-7.
[83]Hu A, Wang F, Sellers JR. Mutations in human nonmuscle myosin ⅡA found in patients with May-Hegglin anomaly and Fechtner syndrome result in impaired enzymatic function. J Biol Chem.2002,277(48):46512-7.
[84]Ghiggeri GM, Caridi G, Magrini U, et al. Genetics, clinical and pathological features of glomerulonephritis associated with mutations of nonmuscle myosin ⅡA (Fechtner syndrome). Am J Kidney Dis.2003,41(1):95-104.
[85]Kriajevska MV, Cardenas MN, Grigorian MS, et al. Non-muscle myosin heavy chain as a possible target for protein encoded by metastasis-related mts-1 gene. J Biol Chem.1994,269(31):19679-82.
[86]Tarabykina S, Griffiths TR, Tulchinsky E, et al. Metastasis-associated protein S100A4:spotlight on its role in cell migration. Curr Cancer Drug Targets.2007,7(3):217-28.
[87]Wang HY, Zhang JY, Cui JT, et al. Expression status of S100A14 and S100A4 correlates with metastatic potential and clinical outcome in colorectal cancer after surgery. Oncol Rep.2010,23(1):45-52.
[88]Wang YY, Ye ZY, Zhao ZS, et al. High-level expression of S100A4 correlates with lymph node metastasis and poor prognosis in patients with gastric cancer. Ann Surg Oncol.2010,17(1):89-97.
[89]Tabata T, Tsukamoto N, Fooladi AA, et al. RNA interference targeting against S100A4 suppresses cell growth and motility and induces apoptosis in human pancreatic cancer cells. Biochem Biophys Res Commun.2009,390(3):475-80.
[90]Ismail NI, Kaur G, Hashim H, et al. S100A4 overexpression proves to be independent marker for breast cancer progression. Cancer Cell Int.2008,8:12.
[91]Ninomiya I, Ohta T, Fushida S, et al. Increased expression of S100A4 and its prognostic significance in esophageal squamous cell carcinoma. Int J Oncol.2001,18(4):715-20.
[92]Tsuna M, Kageyama S, Fukuoka J, et al. Significance of S100A4 as a prognostic marker of lung squamous cell carcinoma. Anticancer Res.2009,29(7):2547-54.
[93]Donato R. Intracellular and extracellular roles of S100 proteins. Microsc Res Tech.2003,60(6):540-51.
[94]Kim EJ, Helfman DM. Characterization of the metastasis-associated protein, S100A4. Roles of calcium binding and dimerization in cellular localization and interaction with myosin. J Biol Chem.2003,278(32):30063-73.
[95]Cohen C, Parry DA. A conserved C-terminal assembly region in paramyosin and myosin rods. J Struct Biol.1998,122(1-2):180-7.
[96]Ismail TM, Fernig DG, Rudland PS, et al. The basic C-terminal amino acids of calcium-binding protein S100A4 promote metastasis. Carcinogenesis.2008,29(12):2259-66.
[97]Hua J, Chen D, Fu H, et al. Short hairpin RNA-mediated inhibition of S100A4 promotes apoptosis and suppresses proliferation of BGC823 gastric cancer cells in vitro and in vivo. Cancer Lett.2009.
[98]Obungu VH, Lee Burns A, Agarwal SK, et al. Menin, a tumor suppressor, associates with nonmuscle myosin Ⅱ-A heavy chain. Oncogene.2003,22(41):6347-58.
[99]Wei Q, Adelstein RS. Conditional expression of a truncated fragment of nonmuscle myosin Ⅱ-A alters cell shape but not cytokinesis in HeLa cells. Mol Biol Cell.2000,11(10):3617-27.
[100]Huang Y, Arora P, McCulloch CA, et al. The collagen receptor DDR1 regulates cell spreading and motility by associating with myosin Ⅱ A. J Cell Sci.2009,122(Pt 10):1637-46.
[101]Vogel WF, Abdulhussein R, Ford CE. Sensing extracellular matrix:an update on discoidin domain receptor function. Cell Signal.2006,18(8):1108-16.
[102]Yoshimura T, Matsuyama W, Kamohara H. Discoidin domain receptor 1:a new class of receptor regulating leukocyte-collagen interaction. Immunol Res.2005,31(3):219-30.
[103]Huang Y, Shi H, Zhou H, et al. The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin. Blood.2006,107(9):3564-71.
[104]Hosaka K, Takeda T, Ⅱ no N, et al. Megalin and nonmuscle myosin heavy chain ⅡA interact with the adaptor protein Disabled-2 in proximal tubule cells. Kidney Int.2009,75(12):1308-15.
[105]Bao J, Jana SS, Adelstein RS. Vertebrate nonmuscle myosin Ⅱ isoforms rescue small interfering RNA-induced defects in COS-7 cell cytokinesis. J Biol Chem.2005,280(20):19594-9.
[106]Maeda J, Hirano T, Ogiwara A, et al. Proteomic analysis of stage I primary lung adenocarcinoma aimed at individualisation of postoperative therapy. Br J Cancer.2008,98(3):596-603.
[107]Butcher DT, Alliston T, Weaver VM. A tense situation:forcing tumour progression. Nat Rev Cancer.2009,9(2):108-22.
[2]中华人民共和国卫生部《2009中国卫生统计年鉴》,2009：254.
[3]Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med.2003, 349(23):2241-52.
[4]Fumoto S, Shimokuni T, Tanimoto K, et al. Selection of a novel drug-response predictor in esophageal cancer:A novel screening method using microarray and identification of IFITM1 as a potent marker gene of CDDP response. Int J Oncol.2008,32(2):413-23.
[5]Vogelstein B., Kinzler K.W. Cancer genes and the pathways they control. Nat Med 2004,10:789-99.
[6]Grimsrud PA, Swaney DL, Wenger CD, et al. Phosphoproteomics for the masses. ACS Chem Biol.2010,5(1):105-19.
[7]Johnson SA, Hunter T. Kinomics:methods for deciphering the kinome. Nat Meth.2005,2(1):17-25.
[8]Manning G, Whyte DB, Martinez R, et al. The protein kinase complement of the human genome. Science.2002,298(5600):1912-34.
[9]Michael Deininger, Tyrosine Kinase Inhibitors[A] Gewirtz DA., Holt S.E., Grant S. Cancer Drμg Discovery and Development Apoptosis, Senescence, and Cancer[M]. Humana Press,2007,477-508.
[10]Mayya V, Han DK. Phosphoproteomics by mass spectrometry:insights, implications, applications and limitations. Expert Rev Proteomics.2009,6(6):605-18.
[11]Hunter T. Signaling-2000 and beyond. Cell.2000,100(1):113-27.
[12]Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell.2000,103(2):211-25.
[13]Hunter T. Tyrosine phosphorylation:thirty years and counting. Curr Opin Cell Biol.2009,21(2):140-6.
[14]Pande AU, Iyer RV, Rani A, et al. Epidermal growth factor receptor-directed therapy in esophageal cancer. Oncology-basel.2007,73(5-6):281-9.
[15]Hara F, Aoe M, Doihara H, et al. Antitumor effect of gefitinib ('Iressa') on esophageal squamous cell carcinoma cell lines in vitro and in vivo. Cancer Lett.2005,226(1):37-47.
[16]Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA, et al. Predictive factors for outcome in a phase Ⅱ study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol.2006,24(10):1612-9.
[17]Guo M, Liu S, Herman JG, et al. Gefitinib-sensitizing mutation in esophageal carcinoma cell line Kyse450. Cancer Biol Ther.2006,5(2):152-5.
[18]Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell.2007,131(6):1190-203.
[19]Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature.2007,448(7153):561-6.
[20]Meyerson M. Cancer:broken genes in solid tumours. Nature.2007,448(7153):545-6.
[21]Chong PK, Lee H, Kong JW, et al. Phosphoproteomics, oncogenic signaling and cancer research. Proteomics.2008,8(21):4370-82.
[22]Pawson T, Scott JD. Protein phosphorylation in signaling-50 years and counting. Trends Biochem Sci.2005,30(6):286-90.
[23]Moran MF, Tong J, Taylor P, et al. Emerging applications for phospho-proteomics in cancer molecular therapeutics. Biochim Biophys Acta.2006,1766(2):230-41.
[24]Ashman K, Villar EL. Phosphoproteomics and cancer research. Clin Transl Oncol.2009,11(6):356-62.
[25]Paradela A, Albar JP. Advances in the analysis of protein phosphorylation. J Proteome Res.2008,7 (5):1809-18.
[26]Olsen JV, Vermeulen M, Santamaria A, et al. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal.2010,3(104):ra3.
[27]Schreiber TB, Mausbacher N, Breitkopf SB, et al. Quantitative phosphoproteomics-an emerging key technology in signal-transduction research. Proteomics.2008,8(21):4416-32.
[28]Preisinger C, von Kriegsheim A, Matallanas D, et al. Proteomics and phosphoproteomics for the mapping of cellular signalling networks. Proteomics.2008,8(21):4402-15.
[29]Leroy C, Fialin C, Sirvent A, et al. Quantitative phosphoproteomics reveals a cluster of tyrosine kinases that mediates SRC invasive activity in advanced colon carcinoma cells. Cancer Res.2009,69(6):2279-86.
[30]Beausoleil SA, Jedrychowski M, Schwartz D, et al. Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A.2004,101(33):12130-5.
[31]Ficarro S, Chertihin O, Westbrook VA, et al. Phosphoproteome analysis of capacitated human sperm. Evidence of tyrosine phosphorylation of a kinase-anchoring protein 3 and valosin-containing protein/p97 during capacitation. J Biol Chem.2003,278(13):11579-89.
[32]Simons M, Wang M, McBride OW, et al. Human nonmuscle myosin heavy chains are encoded by two genes located on different chromosomes. Circ Res.1991,69(2):530-9.
[33]Toothaker L, Gonzalez D, Tung N, et al. Cellular myosin heavy chain in human leukocytes:isolation of 5'cDNA clones, characterization of the protein, chromosomal localization, and upregulation during myeloid differentiation. Blood.1991,78(7):1826-33.
[34]Vicente-Manzanares M, Ma X, Adelstein RS, et al. Non-muscle myosin Ⅱ takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol.2009,10(11):778-90.
[35]Conti MA, Even-Ram S, Liu C, et al. Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain Ⅱ-A in mice. J Biol Chem.2004,279(40):41263-6.
[36]Kelley MJ, Jawien W, Ortel TL, et al. Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly. Nat Genet.2000,26(1):106-8.
[37]Seri M, Cusano R, Gangarossa S, et al. Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium. Nat Genet.2000,26(1):103-5.
[38]Kunishima S, Kojima T, Matsushita T, et al. Mutations in the NMMHC-A gene cause autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly/Sebastian syndrome). Blood.2001,97(4):1147-9.
[39]Ozsahinog, lu C, Kumi M, et al. Hereditary macrothrombocytopathia, deafness and nephritis (Epstein's triad). Int J Pediatr Otorhi.1985,9(3):257-61.
[40]Peterson L, Rao K, Crosson J, et al. Fechtner syndrome-a variant of Alport's syndrome with leukocyte inclusions and macrothrombocytopenia. Blood.1985,65(2):397-406.
[41]Greinacher A, Nieuwenhuis HK, White JG. Sebastian platelet syndrome:A new variant of hereditary macrothrombocytopenia with leukocyte inclusions. Ann Hematol.1990,61(5):282-8.
[42]Ludowyke RI, Elgundi Z, Kranenburg T, et al. Phosphorylation of nonmuscle myosin heavy chain ⅡA on Ser1917 is mediated by protein kinase C beta Ⅱ and coincides with the onset of stimulated degranulation of RBL-2H3 mast cells. J Immunol.2006,177(3):1492-9.
[43]Murakami N, Chauhan VP, Elzinga M. Two nonmuscle myosin Ⅱ heavy chain isoforms expressed in rabbit brains:filament forming properties, the effects of phosphorylation by protein kinase C and casein kinase Ⅱ, and location of the phosphorylation sites. Biochemistry-us.1998,37(7):1989-2003.
[44]Clark K, Middelbeek J, Dorovkov MV, et al. The alpha-kinases TRPM6 and TRPM7, but not eEF-2 kinase, phosphorylate the assembly domain of myosin ⅡA, ⅡB and ⅡC. Febs Lett.2008,582(20):2993-7.
[45]Clark K, Middelbeek J, Lasonder E, et al. TRPM7 regulates myosin ⅡA filament stability and protein localization by heavy chain phosphorylation. J Mol Biol.2008,378(4):790-803.
[46]Minamiya Y, Nakagawa T, Saito H, et al. Increased expression of myosin light chain kinase mRNA is related to metastasis in non-small cell lung cancer. Tumour Biol.2005,26(3):153-7.
[47]Barkan D, Kleinman H, Simmons JL, et al. Inhibition of Metastatic Outgrowth from Single Dormant Tumor Cells by Targeting the Cytoskeleton. Cancer Res.2008,68(15):6241-50.
[48]Dulyaninova NG, House RP, Betapudi V, et al. Myosin-IIA heavy-chain phosphorylation regulates the motility of MDA-MB-231 carcinoma cells. Mol Biol Cell.2007,18(8):3144-55.
[49]Dulyaninova NG, Malashkevich VN, Almo SC, et al. Regulation of myosin-IIA assembly and Mtsl binding by heavy chain phosphorylation. Biochemistry-us.2005,44(18):6867-76.
[50]Li ZH, Spektor A, Varlamova O, et al. Mts1 regulates the assembly of nonmuscle myosin-ⅡA. Biochemistry-us.2003,42(48):14258-66.
[51]Ismail TM, Fernig DG, Rudland PS, et al. The basic C-terminal amino acids of calcium-binding protein S100A4 promote metastasis. Carcinogenesis.2008,29(12):2259-66.
[52]Johnson JD, Edman JC, Rutter WJ. A receptor tyrosine kinase found in breast carcinoma cells has an extracellular discoidin I-like domain. Proc Natl Acad Sci U S A.1993,90(12):5677-81.
[53]Abdulhussein R, Koo DH, Vogel WF. Identification of disulfide-linked dimers of the receptor tyrosine kinase DDR1. J Biol Chem.2008,283(18):12026-33.
[54]Yoshimura T, Matsuyama W, Kamohara H. Discoidin domain receptor 1:a new class of receptor regulating leukocyte-collagen interaction. Immunol Res.2005,31(3):219-30.
[55]Vogel WF, Abdulhussein R, Ford CE. Sensing extracellular matrix:an update on discoidin domain receptor function. Cell Signal.2006,18(8):1108-16.
[56]Wang CZ, Yeh YC, Tang MJ. DDR1/E-cadherin complex regulates the activation of DDR1 and cell spreading. Am J Physiol Cell Physiol.2009,297(2):C419-29.
[57]Yoshida D, Teramoto A. Enhancement of pituitary adenoma cell invasion and adhesion is mediated by discoidin domain receptor-1. J Neurooncol.2007,82(1):29-40.
[58]Nemoto T, Ohashi K, Akashi T, et al. Overexpression of protein tyrosine kinases in human esophageal cancer. Pathobiology.1997,65(4):195-203.
[59]李超,向小勇,陈力,等.DDR1蛋白在食管鳞癌组织中的表达及临床意义.内分泌外科杂志.2007,1(4)：252-4.
[60]Davies H, Hunter C, Smith R, et al. Somatic Mutations of the Protein Kinase Gene Family in Human Lung Cancer. Cancer Res.2005,65(17):7591-5.
[61]Ford CE, Lau SK, Zhu CQ, et al. Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma. Br J Cancer.2007,96(5):808-14.
[62]Huang Y, Arora P, McCulloch CA, et al. The collagen receptor DDR1 regulates cell spreading and motility by associating with myosin ⅡA. J Cell Sci.2009,122(Pt 10):1637-46.
[63]Faraci-Orf E, McFadden C, Vogel WF. DDR1 signaling is essential to sustain Stat5 function during lactogenesis. J Cell Biochem.2006,97(1):109-21.
[64]Seri M, Pecci A, Di Bari F, et al. MYH9-related disease:May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore).2003,82(3):203-15.
[65]Kunishima S, Matsushita T, Kojima T, et al. Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions. J Hum Genet.2001,46(12):722-9.
[66]Maeda J, Hirano T, Ogiwara A, et al. Proteomic analysis of stage I primary lung adenocarcinoma aimed at individualisation of postoperative therapy. Br J Cancer.2008,98(3):596-603.
[67]Dong F, Li S, Pujol-Moix N, et al. Genotype-phenotype correlation in MYH9-related thrombocytopenia. Br J Haematol.2005,130(4):620-7.
[68]Kunishima S, Matsushita T, Yoshihara T, et al. First description of somatic mosaicism in MYH9 disorders. Br J Haematol.2005,128(3):360-5.
[69]Kunishima S, Takaki K, Ito Y, et al. Germinal mosaicism in MYH9 disorders:a family with two affected siblings of normal parents. Br J Haematol.2009,145(2):260-2.
[70]Jia ZL, Li Y, Chen CH, et al. Association among polymorphisms at MYH9, environmental factors, and nonsyndromic orofacial clefts in western China. Dna Cell Biol.2010,29(1):25-32.
[71]Nunez M, Saran AM, Freedman BI. Gene-gene and gene-environment interactions in HIV-associated nephropathy:A focus on the MYH9 nephropathy susceptibility gene. Adv Chronic Kidney Dis.2010,17(1):44-51.
[72]Sekine T, Konno M, Sasaki S, et al. Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease. Kidney Int.2010.
[73]Winkler CA, Nelson G, Oleksyk TK, et al. Genetics of focal segmental glomerulosclerosis and human immunodeficiency virus-associated collapsing glomerulopathy:the role of MYH9 genetic variation. Semin Nephrol.2010,30(2):111-25.
[74]Cai Y, Biais N, Giannone G, et al. Nonmuscle myosin ⅡA-dependent force inhibits cell spreading and drives F-actin flow. Biophys J.2006,91(10):3907-20.
[75]Betapudi V, Licate LS, Egelhoff TT. Distinct roles of nonmuscle myosin Ⅱ isoforms in the regulation of MDA-MB-231 breast cancer cell spreading and migration. Cancer Res.2006,66(9):4725-33.
[76]Duxbury MS, Ashley SW, Whang EE. Inhibition of pancreatic adenocarcinoma cellular invasiveness by blebbistatin:a novel myosin Ⅱ inhibitor. Biochem Biophys Res Commun.2004,313(4):992-7.
[77]Wei Q, Adelstein RS. Conditional expression of a truncated fragment of nonmuscle myosin Ⅱ-A alters cell shape but not cytokinesis in HeLa cells. Mol Biol Cell.2000,11(10):3617-27.
[78]Bao J, Jana SS, Adelstein RS. Vertebrate nonmuscle myosin Ⅱ isoforms rescue small interfering RNA-induced defects in COS-7 cell cytokinesis. J Biol Chem.2005,280(20):19594-9.
[79]Babbin BA, Koch S, Bachar M, et al. Non-muscle myosin ⅡA differentially regulates intestinal epithelial cell restitution and matrix invasion. Am J Pathol.2009,174(2):436-48.
[80]Tarabykina S, Griffiths TR, Tulchinsky E, et al. Metastasis-associated protein S100A4:spotlight on its role in cell migration. Curr Cancer Drμg Targets.2007,7(3):217-28.
[81]Wang HY, Zhang JY, Cui JT, et al. Expression status of S100A14 and S100A4 correlates with metastatic potential and clinical outcome in colorectal cancer after surgery. Oncol Rep.2010,23(1):45-52.
[82]Wang YY, Ye ZY, Zhao ZS, et al. High-level expression of S100A4 correlates with lymph node metastasis and poor prognosis in patients with gastric cancer. Ann Surg Oncol.2010,17(1):89-97.
[83]Tabata T, Tsukamoto N, Fooladi AA, et al. RNA interference targeting against S100A4 suppresses cell growth and motility and induces apoptosis in human pancreatic cancer cells. Biochem Biophys Res Commun.2009,390(3):475-80.
[84]Ismail NI, Kaur G, Hashim H, et al. S100A4 overexpression proves to be independent marker for breast cancer progression. Cancer Cell Int.2008,8:12.
[85]Ninomiya I, Ohta T, Fushida S, et al. Increased expression of S100A4 and its prognostic significance in esophageal squamous cell carcinoma. Int J Oncol.2001,18(4):715-20.
[86]Tsuna M, Kageyama S, Fukuoka J, et al. Significance of S100A4 as a prognostic marker of lung squamous cell carcinoma. Anticancer Res.2009,29(7):2547-54.
[87]Donato R. Intracellular and extracellular roles of S100 proteins. Microsc Res Tech.2003,60(6):540-51.
[88]Kim EJ, Helfman DM. Characterization of the metastasis-associated protein, S100A4. Roles of calcium binding and dimerization in cellular localization and interaction with myosin. J Biol Chem.2003,278(32):30063-73.
[89]Li ZH, Bresnick AR. The S100A4 metastasis factor regulates cellular motility via a direct interaction with myosin-IIA. Cancer Res.2006,66(10):5173-80.
[90]Santamaria-Kisiel L, Rintala-Dempsey AC, Shaw GS. Calcium-dependent and-independent interactions of the S100 protein family. Biochem J.2006,396(2):201-14.
[91]Hua J, Chen D, Fu H, et al. Short hairpin RNA-mediated inhibition of S100A4 promotes apoptosis and suppresses proliferation of BGC823 gastric cancer cells in vitro and in vivo. Cancer Lett.2009.
[92]Heinzelmann-Schwarz VA, Gardiner-Garden M, Henshall SM, et al. Overexpression of the cell adhesion molecules DDR1, Claudin 3, and Ep-CAM in metaplastic ovarian epithelium and ovarian cancer. Clin Cancer Res.2004,10(13):4427-36.
[93]Shimada K, Nakamura M, Ishida E, et al. Prostate cancer antigen-1 contributes to cell survival and invasion thoμgh discoidin receptor 1 in human prostate cancer. Cancer Sci.2008,99(1):39-45.
[94]Weiner HL, Huang H, Zagzag D, et al. Consistent and selective expression of the discoidin domain receptor-1 tyrosine kinase in human brain tumors. Neurosurgery.2000,47(6):1400-9.
[95]Yamanaka R, Arao T, Yajima N, et al. Identification of expressed genes characterizing long-term survival in malignant glioma patients. Oncogene.2006,25(44):5994-6002.
[96]Das S, Ongusaha PP, Yang YS, et al. Discoidin domain receptor 1 receptor tyrosine kinase induces cyclooxygenase-2 and promotes chemoresistance throμgh nuclear factor-kappaB pathway activation. Cancer Res.2006,66(16):8123-30.
[97]Bantscheff M, Eberhard D, Abraham Y, et al. Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat Biotechnol.2007,25(9):1035-44.
[98]Rix U, Hantschel O, Durnberger G, et al. Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood.2007,110(12):4055-63.
[99]Day E, Waters B, Spiegel K, et al. Inhibition of collagen-induced discoidin domain receptor 1 and 2 activation by imatinib, nilotinib and dasatinib. Eur J Pharmacol.2008,599(1-3):44-53.
[100]Conti MA, Adelstein RS. Nonmuscle myosin Ⅱ moves in new directions. J Cell Sci.2008,121(Pt1):11-8.
[101]Poincloux R, Lizarraga F, Chavrier P. Matrix invasion by tumour cells:a focus on MT1-MMP trafficking to invadopodia. J Cell Sci.2009,122(Pt 17):3015-24.
[102]Golomb E, Ma X, Jana SS, et al. Identification and characterization of nonmuscle myosin II-C, a new member of the myosin Ⅱ family. J Biol Chem.2004,279(4):2800-8.
[103]Swailes NT, Colegrave M, Knight PJ, et al. Non-muscle myosins 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse. J Cell Sci.2006,119(Pt 17):3561-70.
[104]Yuen SL, Ogut O, Brozovich FV. Nonmuscle myosin is regulated during smooth muscle contraction. Am J Physiol Heart Circ Physiol.2009,297(1):H191-9.
[105]Morano I, Chai G-X, Baltas LG, et al. Smooth-muscle contraction without smooth-muscle myosin. Nat Cell Biol.2000,2(6):371-5.
[106]Edwards RA. Laser capture microdissection of mammalian tissue. J Vis Exp.2007(8):309.
[107]Mustafa D, Kros JM, Luider T. Combining laser capture microdissection and proteomics techniques. Methods Mol Biol.2008,428:159-78.
[108]Liu Y, Wu J, Yan G, et al. Proteomic analysis of prolactinoma cells by immuno-laser capture microdissection combined with online two-dimensional nano-scale liquid chromatography/mass spectrometry. Proteome Sci.2010,8:2.
[109]Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature.1998,391 (6669):806-11.
[110]Kaiser JP, Reinmann A, Bruinink A. The effect of topographic characteristics on cell migration velocity. Biomaterials.2006,27(30):5230-41.
[111]Gupton SL, Waterman-Storer CM. Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration. Cell.2006,125(7):1361-74.
[112]Rhee S. Fibroblasts in three dimensional matrices:cell migration and matrix remodeling. Exp Mol Med.2009,41(12):858-65.
[113]Green JA, Yamada KM. Three-dimensional microenvironments modulate fibroblast signaling responses. Adv Drug Deliv Rev.2007,59(13):1293-8.
[114]Li Y, Friedmann DR, Mhatre AN, et al. MYH9-siRNA and MYH9 mutant alleles:expression in cultured cell lines and their effects upon cell structure and function. Cell Motil Cytoskeleton.2008,65(5):393-405.
[115]Jana SS, Kawamoto S, Adelstein RS. A specific isoform of nonmuscle myosin II-C is required for cytokinesis in a tumor cell line. J Biol Chem.2006,281(34):24662-70.
[116]Beadle C, Assanah MC, Monzo P, et al. The role of myosin II in glioma invasion of the brain. Mol Biol Cell.2008,19(8):3357-68.
[117]Limouze J, Straight AF, Mitchison T, et al. Specificity of blebbistatin, an inhibitor of myosin Ⅱ. J Muscle Res Cell Motil.2004,25(4-5):337-41.
[118]Vicente-Manzanares M, Koach MA, Whitmore L, et al. Segregation and activation of myosin ⅡB creates a rear in migrating cells. J Cell Biol.2008,183(3):543-54.
[119]Zaidel-Bar R, Ballestrem C, Kam Z, et al. Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells. J Cell Sci.2003,116(Pt22):4605-13.
[120]Yamazaki D, Kurisu S, Takenawa T. Regulation of cancer cell motility through actin reorganization. Cancer Sci.2005,96(7):379-86.
[121]Lauffenburger DA, Horwitz AF. Cell migration:a physically integrated molecular process. Cell.1996,84(3):359-69.
[122]Vicente-Manzanares M, Zareno J, Whitmore L, et al. Regulation of protrusion, adhesion dynamics, and polarity by myosins ⅡA and ⅡB in migrating cells. J Cell Biol.2007,176(5):573-80.
[123]Sandquist JC, Swenson KI, DeMali KA, et al. Rho Kinase Differentially Regulates Phosphorylation of Nonmuscle Myosin Ⅱ Isoforms A and B during Cell Rounding and Migration. J Biol Chem.2006,281(47):35873-83.
[124]Even-Ram S, Doyle AD, Conti MA, et al. Myosin ⅡA regulates cell motility and actomyosin-microtubule crosstalk. Nat Cell Biol.2007,9(3):299-309.
[1]Odronitz F, Kollmar M. Drawing the tree of eukaryotic life based on the analysis of 2,269 manually annotated myosins from 328 species. Genome Biol.2007,8(9):R196.
[2]Sellers JR. Myosins:a diverse superfamily. Biochim Biophys Acta.2000,1496(1):3-22.
[3]Golomb E, Ma X, Jana SS, et al. Identification and characterization of nonmuscle myosin Ⅱ-C, a new member of the myosin Ⅱ family. J Biol Chem.2004,279(4):2800-8.
[4]Swailes NT, Colegrave M, Knight PJ, et al. Non-muscle myosins 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse. J Cell Sci.2006,119(Pt 17):3561-70.
[5]Yuen SL, Ogut O, Brozovich FV. Nonmuscle myosin is regulated during smooth muscle contraction. Am J Physiol Heart Circ Physiol.2009,297(1):H191-9.
[6]Morano I, Chai G-X, Baltas LG, et al. Smooth-muscle contraction without smooth-muscle myosin. Nat Cell Biol.2000,2(6):371-5.
[7]Uren D, Hwang HK, Hara Y, et al. Gene dosage affects the cardiac and brain phenotype in nonmuscle myosin Ⅱ-B-depleted mice. J Clin Invest.2000,105(5):663-71.
[8]Simons M, Wang M, McBride OW, et al. Human nonmuscle myosin heavy chains are encoded by two genes located on different chromosomes. Circ Res.1991,69(2):530-9.
[9]Toothaker L, Gonzalez D, Tung N, et al. Cellular myosin heavy chain in human leukocytes:isolation of 5' cDNA clones, characterization of the protein, chromosomal localization, and upregulation during myeloid differentiation. Blood.1991,78(7):1826-33.
[10]Maupin P, Phillips CL, Adelstein RS, et al. Differential localization of myosin-Ⅱ isozymes in human cultured cells and blood cells. J Cell Sci.1994,107 (Pt 11):3077-90.
[11]Rochlin MW, Itoh K, Adelstein RS, et al. Localization of myosin Ⅱ A and B isoforms in cultured neurons. J Cell Sci.1995,108 (Pt 12):3661-70.
[12]Straussman R, Ben-Ya'acov A, Woolfson DN, et al. Kinking the coiled coil-negatively charged residues at the coiled-coil interface. J Mol Biol.2007,366(4):1232-42.
[13]Svitkina TM, Verkhovsky AB, Borisy GG. Improved procedures for electron microscopic visualization of the cytoskeleton of cultured cells. J Struct Biol.1995,115(3):290-303.
[14]Scholey JM, Taylor KA, Kendrick-Jones J. Regulation of non-muscle myosin assembly by calmodulin-dependent light chain kinase. Nature.1980,287(5779):233-5.
[15]Vicente-Manzanares M, Koach MA, Whitmore L, et al. Segregation and activation of myosin ⅡB creates a rear in migrating cells. J Cell Biol.2008,183(3):543-54.
[16]Jung HS, Komatsu S, Ikebe M, et al. Head-head and head-tail interaction:a general mechanism for switching off myosin Ⅱ activity in cells. Mol Biol Cell.2008,19(8):3234-42.
[17]Craig R, Woodhead JL. Structure and function of myosin filaments. Curr Opin Struct Biol.2006,16(2):204-12.
[18]Vicente-Manzanares M, Ma X, Adelstein RS, et al. Non-muscle myosin Ⅱ takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol.2009,10(11):778-90.
[19]Kim KY, Kovacs M, Kawamoto S, et al. Disease-associated mutations and alternative splicing alter the enzymatic and motile activity of nonmuscle myosins Ⅱ-B and Ⅱ-C. J Biol Chem.2005,280(24):22769-75.
[20]Bao J, Ma X, Liu C, et al. Replacement of nonmuscle myosin Ⅱ-B with Ⅱ-A rescues brain but not cardiac defects in mice. J Biol Chem.2007,282(30):22102-11.
[21]Nakasawa T, Takahashi M, Matsuzawa F, et al. Critical regions for assembly of vertebrate nonmuscle myosin Ⅱ. Biochemistry-us.2005,44(1):174-83.
[22]Sandquist JC, Means AR. The C-terminal tail region of nonmuscle myosin Ⅱ directs isoform-specific distribution in migrating cells. Mol Biol Cell.2008,19(12):5156-67.
[23]Ikebe M. Phosphorylation of a second site for myosin light chain kinase on platelet myosin. Biochemistry-us.1989,28(22):8750-5.
[24]Somlyo AP, Somlyo AV. Ca2+sensitivity of smooth muscle and nonmuscle myosin Ⅱ:modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev.2003,83(4):1325-58.
[25]Hirata N, Takahashi M, Yazawa M. Diphosphorylation of regulatory light chain of myosin ⅡA is responsible for proper cell spreading. Biochem Biophys Res Commun.2009,381(4):682-7.
[26]Matsumura F. Regulation of myosin Ⅱ during cytokinesis in higher eukaryotes. Trends Cell Biol.2005,15(7):371-7.
[27]Zhao ZS, Manser E. PAK and other Rho-associated kinases-effectors with surprisingly diverse mechanisms of regulation. Biochem J.2005,386(Pt 2):201-14.
[28]Kimura K, Ito M, Amano M, et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science.1996,273(5272):245-8.
[29]Sandquist JC, Swenson KI, DeMali KA, et al. Rho Kinase Differentially Regulates Phosphorylation of Nonmuscle Myosin Ⅱ Isoforms A and B during Cell Rounding and Migration. J Biol Chem.2006,281(47):35873-83.
[30]Totsukawa G, Yamakita Y, Yamashiro S, et al. Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts. J Cell Biol.2000,150(4):797-806.
[31]Totsukawa G, Wu Y, Sasaki Y, et al. Distinct roles of MLCK and ROCK in the regulation of membrane protrusions and focal adhesion dynamics during cell migration of fibroblasts. J Cell Biol.2004,164(3):427-39.
[32]Burridge K, Wennerberg K. Rho and Rac take center stage. Cell.2004,116(2):167-79.
[33]Garcia-Mata R, Burridge K. Catching a GEF by its tail. Trends Cell Biol.2007,17(1):36-43.
[34]IKebe M, Reardon S. Phosphorylation of bovine platelet myosin by protein kinase C. Biochemistry-us.1990,29(11):2713-20.
[35]Komatsu S, IKebe M. The phosphorylation of myosin Ⅱ at the Ser1 and Ser2 is critical for normal platelet-derived growth factor induced reorganization of myosin filaments. Mol Biol Cell.2007,18(12):5081-90.
[36]Ludowyke RI, Elgundi Z, Kranenburg T, et al. Phosphorylation of nonmuscle myosin heavy chain ⅡA on Ser1917 is mediated by protein kinase C beta Ⅱ and coincides with the onset of stimulated degranulation of RBL-2H3 mast cells. J Immunol.2006,177(3):1492-9.
[37]Murakami N, Chauhan VP, Elzinga M. Two nonmuscle myosin Ⅱ heavy chain isoforms expressed in rabbit brains:filament forming properties, the effects of phosphorylation by protein kinase C and casein kinase Ⅱ, and location of the phosphorylation sites. Biochemistry-us.1998,37(7):1989-2003.
[38]Dulyaninova NG, Malashkevich VN, Almo SC, et al. Regulation of myosin-ⅡA assembly and Mtsl binding by heavy chain phosphorylation. Biochemistry-us.2005,44(18):6867-76.
[39]Li ZH, Spektor A, Varlamova O, et al. Mts1 regulates the assembly of nonmuscle myosin-Ⅱ A. Biochemistry-us.2003,42(48):14258-66.
[40]Li ZH, Bresnick AR. The S100A4 metastasis factor regulates cellular motility via a direct interaction with myosin-Ⅱ A. Cancer Res.2006,66(10):5173-80.
[41]Clark K, Middelbeek J, Dorovkov MV, et al. The alpha-kinases TRPM6 and TRPM7, but not eEF-2 kinase, phosphorylate the assembly domain of myosin Ⅱ A, ⅡB and ⅡC. Febs Lett.2008,582(20):2993-7.
[42]Clark K, Middelbeek J, Lasonder E, et al. TRPM7 regulates myosin ⅡA filament stability and protein localization by heavy chain phosphorylation. J Mol Biol.2008,378(4):790-803.
[43]Mseka T, Bamburg JR, Cramer LP. ADF/cofilin family proteins control formation of oriented actin-filament bundles in the cell body to trigger fibroblast polarization. J Cell Sci.2007,120(Pt 24):4332-44.
[44]Yam PT, Wilson CA, Ji L, et al. Actin-myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility. J Cell Biol.2007,178(7):1207-21.
[45]Vicente-Manzanares M, Zareno J, Whitmore L, et al. Regulation of protrusion, adhesion dynamics, and polarity by myosins ⅡA and ⅡB in migrating cells. J Cell Biol.2007,176(5):573-80.
[46]Cai Y, Biais N, Giannone G, et al. Nonmuscle myosin Ⅱ A-dependent force inhibits cell spreading and drives F-actin flow. Biophys J.2006,91(10):3907-20.
[47]Even-Ram S, Doyle AD, Conti MA, et al. Myosin ⅡA regulates cell motility and actomyosin-microtubule crosstalk. Nat Cell Biol.2007,9(3):299-309.
[48]Lauffenburger DA, Horwitz AF. Cell migration:a physically integrated molecular process. Cell.1996,84(3):359-69.
[49]Ridley AJ, Schwartz MA, Burridge K, et al. Cell migration:integrating signals from front to back. Science.2003,302(5651):1704-9.
[50]Small JV, Resch GP. The comings and goings of actin:coupling protrusion and retraction in cell motility. Curr Opin Cell Biol.2005,17(5):517-23.
[51]Kaverina I, Krylyshkina O, Small JV. Regulation of substrate adhesion dynamics during cell motility. Int J Biochem Cell Biol.2002,34(7):746-61.
[52]Gupton SL, Waterman-Storer CM. Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration. Cell.2006,125(7):1361-74.
[53]Webb DJ, Donais K, Whitmore LA, et al. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol.2004,6(2):154-61.
[54]Giannone G, Dubin-Thaler BJ, Rossier O, et al. Lamellipodial actin mechanically links myosin activity with adhesion-site formation. Cell.2007,128(3):561-75.
[55]Betapudi V, Licate LS, Egelhoff TT. Distinct roles of nonmuscle myosin Ⅱ isoforms in the regulation of MDA-MB-231 breast cancer cell spreading and migration. Cancer Res.2006,66(9):4725-33.
[56]Beadle C, Assanah MC, Monzo P, et al. The role of myosin Ⅱ in glioma invasion of the brain. Mol Biol Cell.2008,19(8):3357-68.
[57]Babbin BA, Koch S, Bachar M, et al. Non-muscle myosin ⅡA differentially regulates intestinal epithelial cell restitution and matrix invasion. Am J Pathol.2009,174(2):436-48.
[58]Conti MA, Even-Ram S, Liu C, et al. Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain Ⅱ-A in mice. J Biol Chem.2004,279(40):41263-6.
[59]Ivanov AI, McCall IC, Parkos CA, et al. Role for actin filament turnover and a myosin Ⅱ motor in cytoskeleton-driven disassembly of the epithelial apical junctional complex. Mol Biol Cell.2004,15(6):2639-51.
[60]Ivanov AI, Bachar M, Babbin BA, et al. A unique role for nonmuscle myosin heavy chain ⅡA in regulation of epithelial apical junctions. PLoS One.2007,2(7):e658.
[61]Shewan AM, Maddugoda M, Kraemer A, et al. Myosin 2 is a key Rho kinase target necessary for the local concentration of E-cadherin at cell-cell contacts. Mol Biol Cell.2005,16(10):4531-42.
[62]Yamada S, Nelson WJ. Localized zones of Rho and Rac activities drive initiation and expansion of epithelial cell-cell adhesion. J Cell Biol.2007,178(3):517-27.
[63]Carmona-Fontaine C, Matthews HK, Kuriyama S, et al. Contact inhibition of locomotion in vivo controls neural crest directional migration. Nature.2008,456(7224):957-61.
[64]Kelley MJ, Jawien W, Ortel TL, et al. Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly. Nat Genet.2000,26(1):106-8.
[65]Seri M, Cusano R, Gangarossa S, et al. Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium. Nat Genet.2000,26(1):103-5.
[66]Kunishima S, Kojima T, Matsushita T, et al. Mutations in the NMMHC-A gene cause autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly/Sebastian syndrome). Blood.2001,97(4):1147-9.
[67]Ozsahinog, lu C, Kiimi M, et al. Hereditary macrothrombocytopathia, deafness and nephritis (Epstein's triad). Int J Pediatr Otorhi.1985,9(3):257-61.
[68]Peterson L, Rao K, Crosson J, et al. Fechtner syndrome-a variant of Alport's syndrome with leukocyte inclusions and macrothrombocytopenia. Blood.1985,65(2):397-406.
[69]Greinacher A, Nieuwenhuis HK, White JG. Sebastian platelet syndrome:A new variant of hereditary macrothrombocytopenia with leukocyte inclusions. Ann Hematol.1990,61(5):282-8.
[70]Seri M, Pecci A, Di Bari F, et al. MYH9-related disease:May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore).2003,82(3):203-15.
[71]Dong F, Li S, Pujol-Moix N, et al. Genotype-phenotype correlation in MYH9-related thrombocytopenia. Br J Haematol.2005,130(4):620-7.
[72]Sekine T, Konno M, Sasaki S, et al. Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease. Kidney Int.2010.
[73]Pecci A, Panza E, Pujol-Moix N, et al. Position of nonmuscle myosin heavy chain ⅡA (NMMHC-ⅡA) mutations predicts the natural history of MYH9-related disease. Hum Mutat.2008,29(3):409-17.
[74]Kunishima S, Matsushita T, Yoshihara T, et al. First description of somatic mosaicism in MYH9 disorders. Br J Haematol.2005,128(3):360-5.
[75]Kunishima S, Takaki K, Ito Y, et al. Germinal mosaicism in MYH9 disorders:a family with two affected siblings of normal parents. Br J Haematol.2009,145(2):260-2.
[76]Burt RA, Joseph JE, Milliken S, et al. Description of a novel mutation leading to MYH9-related disease. Thromb Res.2008,122(6):861-3.
[77]de Rocco D, Heller PG, Girotto G, et al. MYH9 related disease:a novel missense Ala95Asp mutation of the MYH9 gene. Platelets.2009,20(8):598-602.
[78]Pecci A, Panza E, De Rocco D, et al. MYH9 related disease:four novel mutations of the tail domain of myosin-9 correlating with a mild clinical phenotype. Eur J Haematol.2009.
[79]Marigo V, Nigro A, Pecci A, et al. Correlation between the clinical phenotype of MYH9-related disease and tissue distribution of class Ⅱ nonmuscle myosin heavy chains. Genomics.2004,83(6):1125-33.
[80]Kunishima S, Hamaguchi M, Saito H. Differential expression of wild-type and mutant NMMHC-ⅡA polypeptides in blood cells suggests cell-specific regulation mechanisms in MYH9 disorders. Blood.2008,111(6):3015-23.
[81]Canobbio I, Noris P, Pecci A, et al. Altered cytoskeleton organization in platelets from patients with MYH9-related disease. J Thromb Haemost.2005,3(5):1026-35.
[82]Di Pumpo M, Noris P, Pecci A, et al. Defective expression of GPIb/IX/V complex in platelets from patients with May-Hegglin anomaly and Sebastian syndrome. Haematologica.2002,87(9):943-7.
[83]Hu A, Wang F, Sellers JR. Mutations in human nonmuscle myosin ⅡA found in patients with May-Hegglin anomaly and Fechtner syndrome result in impaired enzymatic function. J Biol Chem.2002,277(48):46512-7.
[84]Ghiggeri GM, Caridi G, Magrini U, et al. Genetics, clinical and pathological features of glomerulonephritis associated with mutations of nonmuscle myosin ⅡA (Fechtner syndrome). Am J Kidney Dis.2003,41(1):95-104.
[85]Kriajevska MV, Cardenas MN, Grigorian MS, et al. Non-muscle myosin heavy chain as a possible target for protein encoded by metastasis-related mts-1 gene. J Biol Chem.1994,269(31):19679-82.
[86]Tarabykina S, Griffiths TR, Tulchinsky E, et al. Metastasis-associated protein S100A4:spotlight on its role in cell migration. Curr Cancer Drug Targets.2007,7(3):217-28.
[87]Wang HY, Zhang JY, Cui JT, et al. Expression status of S100A14 and S100A4 correlates with metastatic potential and clinical outcome in colorectal cancer after surgery. Oncol Rep.2010,23(1):45-52.
[88]Wang YY, Ye ZY, Zhao ZS, et al. High-level expression of S100A4 correlates with lymph node metastasis and poor prognosis in patients with gastric cancer. Ann Surg Oncol.2010,17(1):89-97.
[89]Tabata T, Tsukamoto N, Fooladi AA, et al. RNA interference targeting against S100A4 suppresses cell growth and motility and induces apoptosis in human pancreatic cancer cells. Biochem Biophys Res Commun.2009,390(3):475-80.
[90]Ismail NI, Kaur G, Hashim H, et al. S100A4 overexpression proves to be independent marker for breast cancer progression. Cancer Cell Int.2008,8:12.
[91]Ninomiya I, Ohta T, Fushida S, et al. Increased expression of S100A4 and its prognostic significance in esophageal squamous cell carcinoma. Int J Oncol.2001,18(4):715-20.
[92]Tsuna M, Kageyama S, Fukuoka J, et al. Significance of S100A4 as a prognostic marker of lung squamous cell carcinoma. Anticancer Res.2009,29(7):2547-54.
[93]Donato R. Intracellular and extracellular roles of S100 proteins. Microsc Res Tech.2003,60(6):540-51.
[94]Kim EJ, Helfman DM. Characterization of the metastasis-associated protein, S100A4. Roles of calcium binding and dimerization in cellular localization and interaction with myosin. J Biol Chem.2003,278(32):30063-73.
[95]Cohen C, Parry DA. A conserved C-terminal assembly region in paramyosin and myosin rods. J Struct Biol.1998,122(1-2):180-7.
[96]Ismail TM, Fernig DG, Rudland PS, et al. The basic C-terminal amino acids of calcium-binding protein S100A4 promote metastasis. Carcinogenesis.2008,29(12):2259-66.
[97]Hua J, Chen D, Fu H, et al. Short hairpin RNA-mediated inhibition of S100A4 promotes apoptosis and suppresses proliferation of BGC823 gastric cancer cells in vitro and in vivo. Cancer Lett.2009.
[98]Obungu VH, Lee Burns A, Agarwal SK, et al. Menin, a tumor suppressor, associates with nonmuscle myosin Ⅱ-A heavy chain. Oncogene.2003,22(41):6347-58.
[99]Wei Q, Adelstein RS. Conditional expression of a truncated fragment of nonmuscle myosin Ⅱ-A alters cell shape but not cytokinesis in HeLa cells. Mol Biol Cell.2000,11(10):3617-27.
[100]Huang Y, Arora P, McCulloch CA, et al. The collagen receptor DDR1 regulates cell spreading and motility by associating with myosin Ⅱ A. J Cell Sci.2009,122(Pt 10):1637-46.
[101]Vogel WF, Abdulhussein R, Ford CE. Sensing extracellular matrix:an update on discoidin domain receptor function. Cell Signal.2006,18(8):1108-16.
[102]Yoshimura T, Matsuyama W, Kamohara H. Discoidin domain receptor 1:a new class of receptor regulating leukocyte-collagen interaction. Immunol Res.2005,31(3):219-30.
[103]Huang Y, Shi H, Zhou H, et al. The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin. Blood.2006,107(9):3564-71.
[104]Hosaka K, Takeda T, Ⅱ no N, et al. Megalin and nonmuscle myosin heavy chain ⅡA interact with the adaptor protein Disabled-2 in proximal tubule cells. Kidney Int.2009,75(12):1308-15.
[105]Bao J, Jana SS, Adelstein RS. Vertebrate nonmuscle myosin Ⅱ isoforms rescue small interfering RNA-induced defects in COS-7 cell cytokinesis. J Biol Chem.2005,280(20):19594-9.
[106]Maeda J, Hirano T, Ogiwara A, et al. Proteomic analysis of stage I primary lung adenocarcinoma aimed at individualisation of postoperative therapy. Br J Cancer.2008,98(3):596-603.
[107]Butcher DT, Alliston T, Weaver VM. A tense situation:forcing tumour progression. Nat Rev Cancer.2009,9(2):108-22.