多头绒泡菌PSR蛋白的研究
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摘要
SR蛋白(Serine/Arginine-rich protein)是一组结构相关、进化保守的non-snRNP剪接因子,在调节剪接复合体组装和调节pre-mRNA组成型剪接和选择型剪接方面发挥重要作用。多头绒泡菌(Physarum polycephalum)是原核生物与真核生物之间的过渡态真核古生物,但尚未见到多头绒泡菌SR蛋白的研究报道。
本文从多头绒泡菌分离到一个SR类似蛋白cNDA,其编码蛋白的C-端含有一个富含精氨酸/丝氨酸二肽序列(Arginine/Serine motif)的结构域(RS domian),RS domain的N-端毗邻一个SR蛋白激酶锚定结构域(Docking motif),与其它物种SR蛋白的C-端结构类似,故将该蛋白命名为PSR(Physarum SR)。本文以[γ-~(32)P] ATP为底物,通过放射自显影检测了大肠杆菌(E. Coli)表达的多头绒泡菌SR蛋白激酶PSRPK(Physarum Serine/Arginine Protein-specific Kinase)对大肠杆菌表达的PSR及其残缺肽和突变肽的磷酸化作用,发现PSRPK能在体外磷酸化PSR以及拥有完整RS domain和Docking motif的PSR残缺肽。研究还发现,PSRPK磷酸化作用位点位于PSR C-端连续的RS二肽重复序列(5×RS)上,Docking motif在调节PSRPK磷酸化PSR上扮演重要角色,PSRPK的ATP结合区(ATP-binding region, ABR)序列~(62)LGWGHFSTVWLAIDEKNGGREVALK86和丝氨酸/苏氨酸激酶活性位点特征序列(serine/threonine protein kinases active- site signature, AS)~(184(IIHTDLKPENVLL~(196)是影响PSRPK磷酸化PSR的关键序列,Lys~(86)和Asp~(188)分别是ABR和AS序列的关键氨基酸。
进化保守的14-3-3蛋白广泛参与细胞的各种生命活动。已有的研究显示,植物14-3-3蛋白在调节SR蛋白SRp38应答热胁迫时扮演着重要角色。P14-3-3是多头绒泡菌14-3-3类似蛋白。PSR是以P14-3-3为饵蛋白分离的。本文通过FRET检测了PSR与P14-3-3在哺乳动物细胞内的相互作用,发现PSR在细胞内的分布受P14-3-3的调节,与P14-3-3共表达的PSR由聚集在细胞核转变为主要分布在细胞质。酵母双杂交检测结果显示,PSR需要保持其C-端的完整Docking motif和连续的RS重复序列才能与P14-3-3作用;而P14-3-3 C-端的217-237aa肽段和N-端的76-109aa肽段是其与PSR作用的关键序列,C-端的235TS236磷酸化位点是其与PSR作用的关键位点。
SR proteins are a group of structurally related, evolutionary conserved non-snRNP splicing factors, which participate in the maturation of the splieosome. These proteins contain one or two RNA recognition motifs and a C-terminal domain rich in Arg-Ser repeats (RS domain). SR proteins are phosphorylated at numerous serines in the RS domain by the SR-specific protein kinase (SRPK) family of protein kinases. RS domain phosphorylation is necessary for entry of SR proteins into the nucleus, and may also play important roles in alternative splicing, mRNA export, and other processing events. At present, studies regarding SR protein and SRPKs are mainly on higher eukaryotes. In our previous work, we isolated an SR protein kinase PSRPK from Physarum polycephalum, which can phosphorylate the RS domain of ASF/SF2 both in vivo and in vitro. There is no report of SR protein in P. polycephalum.
The aim of this study was to clarify whether SR protein exists in lower eukaryotes, such as P. polycephalum, and to explore its phosphorylation mechanism and interacting proteins. Here, a novel cDNA encoding a serine/arginine (SR)-rich protein, designated PSR, was isolated from the true slime mold P. polycephalum by yeast two hybridization and 5'-RLM-RACE. The deduced amino acid (aa) sequence reveals that PSR contains RS repeats at its C-terminus, similar to the conventional PSRPK substrate ASF/SF2. To study the novel protein, we generated a variety of mutant constructs by PCR and site-directed mutagenesis. Autoradiography indicated that the purified recombinant PSR was phosphorylated by PSRPK in vitro, and the SR-rich domain (aa 460–469) in the PSR protein was required for phosphorylation. In addition, removal of the docking motif (aa 424–450) from PSR significantly reduced the overall catalytic efficiency of the phosphorylation reaction. We also found that the conserved ATP-binding region (ABR) ~(620)LGWGHFSTVWLAIDEKNGGREVALK86 and the serine/threonine protein kinases active-site signature (AS) 184IIHTDLKPENVLL~(196) of PSRPK played a crucial role in substrate phosphorylation, and Lys~(86) and Asp~(188) were crucial for PSRPK phosphorylation of PSR.
14-3-3 proteins associate with phosphorylated SRp38 resulting in protection from dephosphorylation under non-stress conditions, but dissociate in response to heat shock (Shi and Manley, 2007). However, little is known about how the distribution of SR proteins is affected by 14-3-3. To study the interaction between PSR and P14-3-3, we generated a variety of truncated and mutant peptides of PSR and P14-3-3 and co-expression of them in the mammalian cell strain L929 and yeast strain AH109. The distribution of PSR was affected by co-expression with P14-3-3 in the mammalian cell strain L929 using confocal microscopy. Our results demonstrated that P14-3-3 can modulate the distribution of PSR and that the integrated dock motif combined with the RS domain is necessary for PSR interactions with P14-3-3. Furthermore, the peptides 76KGNENHVKRIKEYRNKVEKELSDICQDILNVLD108 (includingα-helix D) and 217YKDSTLIMQLLRDNLTLWTSD237 (includingα-helix I and the phosphorylation site 235ThrSer236) are involved in P14-3-3 interactions with PSR. The phosphorylation site 235ThrSer236 plays a key role in regulating P14-3-3 interactions with phosphorylated PSR, and thereby modulates the distribution of PSR. This study provides further insight into the mechanism of transcriptional regulation of PSR in the true slime mold.
本文从多头绒泡菌分离到一个SR类似蛋白cNDA,其编码蛋白的C-端含有一个富含精氨酸/丝氨酸二肽序列(Arginine/Serine motif)的结构域(RS domian),RS domain的N-端毗邻一个SR蛋白激酶锚定结构域(Docking motif),与其它物种SR蛋白的C-端结构类似,故将该蛋白命名为PSR(Physarum SR)。本文以[γ-~(32)P] ATP为底物,通过放射自显影检测了大肠杆菌(E. Coli)表达的多头绒泡菌SR蛋白激酶PSRPK(Physarum Serine/Arginine Protein-specific Kinase)对大肠杆菌表达的PSR及其残缺肽和突变肽的磷酸化作用,发现PSRPK能在体外磷酸化PSR以及拥有完整RS domain和Docking motif的PSR残缺肽。研究还发现,PSRPK磷酸化作用位点位于PSR C-端连续的RS二肽重复序列(5×RS)上,Docking motif在调节PSRPK磷酸化PSR上扮演重要角色,PSRPK的ATP结合区(ATP-binding region, ABR)序列~(62)LGWGHFSTVWLAIDEKNGGREVALK86和丝氨酸/苏氨酸激酶活性位点特征序列(serine/threonine protein kinases active- site signature, AS)~(184(IIHTDLKPENVLL~(196)是影响PSRPK磷酸化PSR的关键序列,Lys~(86)和Asp~(188)分别是ABR和AS序列的关键氨基酸。
进化保守的14-3-3蛋白广泛参与细胞的各种生命活动。已有的研究显示,植物14-3-3蛋白在调节SR蛋白SRp38应答热胁迫时扮演着重要角色。P14-3-3是多头绒泡菌14-3-3类似蛋白。PSR是以P14-3-3为饵蛋白分离的。本文通过FRET检测了PSR与P14-3-3在哺乳动物细胞内的相互作用,发现PSR在细胞内的分布受P14-3-3的调节,与P14-3-3共表达的PSR由聚集在细胞核转变为主要分布在细胞质。酵母双杂交检测结果显示,PSR需要保持其C-端的完整Docking motif和连续的RS重复序列才能与P14-3-3作用;而P14-3-3 C-端的217-237aa肽段和N-端的76-109aa肽段是其与PSR作用的关键序列,C-端的235TS236磷酸化位点是其与PSR作用的关键位点。
SR proteins are a group of structurally related, evolutionary conserved non-snRNP splicing factors, which participate in the maturation of the splieosome. These proteins contain one or two RNA recognition motifs and a C-terminal domain rich in Arg-Ser repeats (RS domain). SR proteins are phosphorylated at numerous serines in the RS domain by the SR-specific protein kinase (SRPK) family of protein kinases. RS domain phosphorylation is necessary for entry of SR proteins into the nucleus, and may also play important roles in alternative splicing, mRNA export, and other processing events. At present, studies regarding SR protein and SRPKs are mainly on higher eukaryotes. In our previous work, we isolated an SR protein kinase PSRPK from Physarum polycephalum, which can phosphorylate the RS domain of ASF/SF2 both in vivo and in vitro. There is no report of SR protein in P. polycephalum.
The aim of this study was to clarify whether SR protein exists in lower eukaryotes, such as P. polycephalum, and to explore its phosphorylation mechanism and interacting proteins. Here, a novel cDNA encoding a serine/arginine (SR)-rich protein, designated PSR, was isolated from the true slime mold P. polycephalum by yeast two hybridization and 5'-RLM-RACE. The deduced amino acid (aa) sequence reveals that PSR contains RS repeats at its C-terminus, similar to the conventional PSRPK substrate ASF/SF2. To study the novel protein, we generated a variety of mutant constructs by PCR and site-directed mutagenesis. Autoradiography indicated that the purified recombinant PSR was phosphorylated by PSRPK in vitro, and the SR-rich domain (aa 460–469) in the PSR protein was required for phosphorylation. In addition, removal of the docking motif (aa 424–450) from PSR significantly reduced the overall catalytic efficiency of the phosphorylation reaction. We also found that the conserved ATP-binding region (ABR) ~(620)LGWGHFSTVWLAIDEKNGGREVALK86 and the serine/threonine protein kinases active-site signature (AS) 184IIHTDLKPENVLL~(196) of PSRPK played a crucial role in substrate phosphorylation, and Lys~(86) and Asp~(188) were crucial for PSRPK phosphorylation of PSR.
14-3-3 proteins associate with phosphorylated SRp38 resulting in protection from dephosphorylation under non-stress conditions, but dissociate in response to heat shock (Shi and Manley, 2007). However, little is known about how the distribution of SR proteins is affected by 14-3-3. To study the interaction between PSR and P14-3-3, we generated a variety of truncated and mutant peptides of PSR and P14-3-3 and co-expression of them in the mammalian cell strain L929 and yeast strain AH109. The distribution of PSR was affected by co-expression with P14-3-3 in the mammalian cell strain L929 using confocal microscopy. Our results demonstrated that P14-3-3 can modulate the distribution of PSR and that the integrated dock motif combined with the RS domain is necessary for PSR interactions with P14-3-3. Furthermore, the peptides 76KGNENHVKRIKEYRNKVEKELSDICQDILNVLD108 (includingα-helix D) and 217YKDSTLIMQLLRDNLTLWTSD237 (includingα-helix I and the phosphorylation site 235ThrSer236) are involved in P14-3-3 interactions with PSR. The phosphorylation site 235ThrSer236 plays a key role in regulating P14-3-3 interactions with phosphorylated PSR, and thereby modulates the distribution of PSR. This study provides further insight into the mechanism of transcriptional regulation of PSR in the true slime mold.
引文
[1] Utans U, Kramer A. Splicing factor SF4 is dispensable for the assembly of a functional splicing complex and participates in the subsequent steps of the splicing reaction [J]. EMBO J, 1990, 9(12): 4119-4126.
[2] Krainer AR, Conway GC, Kozak D. The essential pre-mRNA splicing factor SF2 influences 5' splice site selection by activating proximal sites [J]. Cell, 1990, 62(1): 35-42.
[3] Ge H, Manley JL. A protein factor, ASF, controls cell-specific alternative splicing of SV40 early pre-mRNA in vitro [J]. Cell, 1990, 62(1): 25-34.
[4] Zuo P, Manley JL. Functional domains of the human splicing factor ASF/SF2 [J]. EMBO J, 1993, 12(12): 4727-4737.
[5] Fu XD, Maniatis T. Factor required for mammalian spliceosome assembly is localized to discrete regions in the nucleus [J]. Nature,1990, 343(6257): 437-441.
[6] Fu XD, Maniatis T. Isolation of a complementary DNA that encodes the mammalian splicing factor SC35 [J]. Science, 1992, 256(5056): 535-538.
[7] Roth MB, Murphy C, Gall JG. A monoclonal antibody that recognizes a phosphorylated epitope stains lampbrush chromosome loops and small granules in the amphibian germinal vesicle [J]. J Cell Biol, 1990, 111: 2217-2223.
[8] Mayeda A, Zahler AM, Krainer AR, Roth MB. Two members of a conserved family of nuclear phosphoproteins are involved in pre-mRNA splicing [J]. Proc Natl Acad Sci USA, 1992, 89(4): 1301-1304.
[9] Roth MB, Zahler AM, Stolk JA. A conserved family of nuclear phosphoproteins localized to sites of polymerase II transcription [J]. J Cell Biol, 1991, 115(3): 587-596.
[10] Zahler AM, Lane WS, Stolk JA, Roth MB. SR proteins: a conserved family of pre-mRNA splicing factors [J]. Genes Dev, 1992, 6(5): 837-847.
[11] Graveley BR. Sorting out the complexity of SR protein functions [J]. RNA, 2000, 6: 1197-1211.
[12] Lazar G, Schaal T, Maniatis T, Goodman HM. Identification of a plant serine-arginine-rich protein similar to the mammalian splicing factor SF2/ASF [J]. Proc Natl Acad Sci USA,1995, 92(17): 7672-7676.
[13] Lopato S, Mayeda A, Krainer AR, Barta A. Pre-mRNA splicing in plants: characterization of Ser/Arg splicing factors [J]. Proc Natl Acad Sci USA, 1996, 93(7): 3074-3079.
[14] Lorkovic ZJ, Barta A. Genome analysis: RNA recognition motif (RRM) and K homology (KH) domain RNA-binding proteins from the flowering plant Arabidopsis thaliana [J]. Nucleic Acids Res, 2002, 30, 623–635.
[15] Jennifer C. LONG, Javier F. CACERES. The SR protein family of splicing factors: master regulators of gene expression [J]. Biochem. J,2009,417:15–27.
[16] Spector DL, Fu XD, Maniatis T. Associations between distinct pre-mRNA splicing components and the cell nucleus [J]. EMBO J. 1991, 10(11): 3467-3481.
[17] Ali GS, Golovkin M, Reddy AS. Nuclear localization and in vivo dynamics of a plant-specific serine/arginine-rich protein [J]. Plant J. 2003, 36(6): 883-893.
[18] Graveley BR, Hertel KJ. SR proteins [M]. In Encyclopedia of Life Sciences. Chichester: John Wiley & Sons; 2005. doi:10.1038/npg.els.0005039.
[19] Liu HX, Zhang M, and Krainer AR. Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins [J]. Gene & Dev. 1998, 12: 1998-2012.
[20] Zuo P, Manley JL. The human splicing factor ASF/SF2 can specifically recognize pre-mRNA 5 splice sites [J]. Proc Natl Acad Sci USA.1994, 91: 3363-3367.
[21] Jamison SF, Pasman Z, Wang J, Will C, Luhrmann R, Manley JL, Garcia-Blanco MA. U1 snRNP-ASF/SF2 interaction and 5' splice site recognition: characterization of required elements [J]. Nucleic Acids Res, 1995, 23(16): 3260-3267.
[22] Liu HX, Chew SL, Cartegni L, Krainer AR. Exonic splicing enhancer motif recognized by human SC35 under splicing conditions [J]. Mol Biol Cell, 2000, 20: 1063-1071.
[23] Forment J, Naranjo MA, Roldan M, Serrano R, Vicente O. Expression of Arabidopsis SR-like splicing proteins confers salt tolerance to yeast and transgenic plants [J]. Plant J, 2002, 30(5): 511-519.
[24] Cáceres JF, Screaton GR, Krainer AR. A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm [J]. Genes Dev, 1998, 12:55-66.
[25] Huang Y, Steitz JA. Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA [J]. Mol Cell, 2001, 7: 899-905.
[26] Lee MS, Henry M, Silver PA. A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export [J]. Genes Dev, 1996, 10:1233-1246.
[27] Gilbert W, Siebel CW, Guthrie C. Phosphorylation by Sky1p promotes Npl3p shuttling and mRNA dissociation [J]. RNA, 2001, 7:302-313.
[28] Blencowe BJ, Nickerson JA, Issner R, et al. Association of nuclear matrix antigens with exon-containing splicing complexes [J]. J Cell Biol, 1994, 127:593-607.
[29] Le Hir H, Moore MJ, Maquat LE. Pre-mRNA splicing alters mRNP composition: evidence for stable association of proteins at exon-exon junctions [J]. Genes Dev, 2000, 14:1098-1108.
[30] Hautbergue GM, Hung ML, Golovanov AP, et al. Mutually exclusive interactions drive handover of mRNA from export adaptors to TAP [J]. Proc Natl Acad Sci USA, 2008, 105:5154-5159.
[31] Karni R, de Stanchina E, Lowe SW, et al. The gene encoding the splicing factor SF2/ASF is a proto-oncogene [J]. Nat Struct Mol Biol, 2007, 14:185-193.
[32] Sanford JR, Gray NK, Beckmann K, Caceres JF. A novel role for shuttling SR proteins in mRNA translation [J]. Genes Dev, 2004, 18:755-768.
[33] Michlewski G, Sanford JR, Caceres JF. The splicing factor SF2/ASF regulates translation initiation by enhancing phosphorylation of 4E-BP1 [J]. Mol Cell, 2008, 3:179-189.
[34] Cao WH, Jamison SF, Garrcia-Blanco MA. Both phosphorylation and dephosphorylation of ASF/SF2 are required for pre-mRNA splicing in vitro [J]. RNA, 1997, 3:1456-1467.
[35] Misteli T, Caceres JF, Clement JQ, Krainer AR, Wilkinson MF, and Spector DL. Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo [J]. J Cell Biol. 1998, 143(2): 297-307.
[36] Xiao SH, Manley JL. Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2 [J]. EMBO J. 1998, 17: 6359-6367.
[37] Koizumi J, Okamoto Y, Onogi H, Mayeda A, Krainer AR., and Hagiwara M. The subcellular localization of SF2/ASF is regulated by direct interaction with SR protein kinases (SRPKs) [J]. J. Biol. Chem. 1999, 274(16): 11125-11131.
[38] Gui JF, Lane WS. A serine kinase regulates intracellular localization of splicing factors in the cell cycle [J]. Nature, 1994, 369(6482): 678-682.
[39] Misteli T, Caceres JF, Clement JQ, et al. Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo [J]. J Cell Biol, 1998, 143(2): 297-307.
[40] Gui JF, Tronchere H. Purification and characterization of a kinase specific for the serine- and arginine-rich pre-mRNA splicing factors [J]. PNAS, 1994, 91(23): 10824-10828.
[41] Wang HY, Lin W. SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells [J]. Cell Biol, 1998, 140(4): 737-750.
[42] Colwill K, Feng LL, Yeakley JM, et al. SRPK1 and Clk/Sty protein kinases show distinct substrate specificities for serine/arginine-rich splicing factors [J]. Biol Chem, 1996, 271(40): 24569-24575.
[43] Tillemans V. Leponce I, Rausin G, et al. Insights into nuclear organization in plants as revealed by the dynamic distribution of Arabidopsis SR splicing factors [J]. Plant Cell ,2006, 18: 3218-3234.
[44] Caceres JF, Screaton GR, Krainer AR. A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm [J]. Genes Dev. 1998, 12:55-56.
[45] Yang L, Lisa J. Embree, Schickwann Tsai, et al. Oncoprotein TLS Interacts with Serine-Arginine Proteins Involved in RNA Splicing [J]. J Biol Chem, 1998, 273: 27761 -27764.48
[46] Aubol BE, Chakrabarti S, Ngo J, et al. Processive phosphorylation of alternative splicing factor/splicing factor 2 [J]. Proc Natl Acad Sci USA. 2003, 100: 12601-12606.
[47] Adolfo VD, Hagopian JC, Ma CT, et al.. Mass spectrometric and kinetic analysis of ASF/SF2 phosphorylation by SRPK1 and Clk/Sty [J]. J Biol Chem. 2005, 280(50): 41761-41768.
[48] Ngo JC, Chakrabarti S, Ding JH, et al. Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 ini regulalted by a Docking motif in ASF/SF2 [J]. Molecular Cell, 2005, 20: 77-89.
[49] Clinton JM, Chansky HA, Odell DD, et al. Characterization and expression of the human gene encoding two translocation liposarcoma protein-associated serine-arginine (TASR) [J] proteins.Gene, 2002, 284: 141-147.
[50] Komatsu M, Kominami E, Arahata K, et al. Cloning and characterization of two neural-salient serine/arginine-rich (NSSR) proteins involved in the regulation of alternativesplicing in neurones [J]. Genes Cells, 1999, 4:593-606.
[51] Woppmann A, Will CL, Kornstadt U, et al. Identification of an snRNP-associated kinase activity that phosphorylates arginine/serine rich domains typical of splicing factors [J]. Nucleic Acids Res, 1993, 21(12): 2815-2822.
[52] Thomas Giannakouros, Eleni Nikolakaki, Ilias Mylonis, et al. Serine-arginine protein kinases: a small protein kinase family with a large cellular presence [J]. FEBS J, 2011, 278: 570–586.
[53] Misteli T, Spector DL. Serine/threonine phosphatase 1 modulates the subnuclear distribution of pre-mRNA splicing factors [J]. Mol Biol Cell, 1996, 7(10): 1559-1572.
[54] Sacco-Bubulya P, Spector DL. Disassembly of interchromatin granule clusters alters the coordination of transcription and pre-mRNA splicing [J]. Cell Biol, 2002, 156(3): 425-436.
[55] Prasanth KV, Sacco-Bubulya PA. Prasanth SG, Spector DL. Sequential entry of components of the gene expression machinery into daughter nuclei [J]. Mol Biol Cell, 2003, 14(3):1043-1057.
[56] Fang Y, Hearn S, Spector DL. Tissue-specific expression and dynamic organization of SR splicing factors in Arabidopsis [J]. Mol Biol Cell. 2004, 15(6): 2664-2673.
[57] Nikolakaki E, Kohen R, Hartmann AM, et al. Cloning and characterization of an alternatively spliced form of SR protein kinase 1 that interacts specifically with scaffold attachment factor-B [J]. J Biol Chem, 2001, 276(43): 40175-40182.
[58] Papoutsopoulou S, Nikolakaki E, Giannakouros T. SRPK1 and LBR protein kinases show identical substrate specificities [J]. BBRC,1999, 255(3): 602-607.
[59] Papoutsopoulou S, Nikolakaki E, Chalepakis G, et al. SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1 [J]. Nucleic Acids Res. 1999, 27(14): 2972-2980.
[60] Daub H, Blencke S, Habenberger P, et al. Identification of SRPK1 and SRPK2 as the major cellular protein kinases phosphorylating hepatitis B virus core protein [J]. Virol, 2001, 76(16): 8124-8137.
[61] Lee CG, Hague LK, Li H, Donnelly R. Identification of toposome, a novel multisubunit complex containing topoisomerase II alpha [J]. Cell Cycle, 2004, 3(5): 638-647.
[62] Thomas Giannakouros, Eleni Nikolakaki, Ilias Mylonis, et al. Serine-arginine proteinkinases: a small protein kinase family with a large cellular presence [J]. FEBS Journal, 2011,278:570–586
[63] Hanks SK, Hunter T. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification [J]. FASEB,1995, 9: 576-596.
[64] Kuroyanagi N, Onogi H. Novel SR-protein-specific kinase, SRPK2, disassembles nuclear speckles [J]. BBRC, 1998, 242(2): 357-364.
[65] Tang Z, Yanagida M. Fission yeast mitotic regulator Dsk1 is an SR protein-specific kinase [J]. Biol Chem, 1998, 273(10): 5963-5969.
[66] Siebel CW, Feng L. Conservation in budding yeast of a kinase specific for SR splicing factors [J]. PNAS, 1999, 96(10): 5440-5445.
[67] Kuroyanagi H, Kimura T. SPK-1, a C. elegans SR protein kinase homologue, is essential for embryogenesis and required for germline development [J]. Mech Dev, 2000, 99(1-2): 51-64.
[68] Portal D, Lobo GS. Trypanosoma cruzi TcSRPK, the first protozoan member of the SRPK family, is biochemically and functionally conserved with metazoan SR protein-specific kinases [J]. Mol Biochem Parasitol, 2003, 127(1): 9-21.
[69] Colwill K, Pawson T. The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution [J]. EMBO J, 1996, 15, 265-275.
[70] Nayler O, Stamm S. Characterization and comparison of four serine- and arginine-rich (SR) protein kinases [J]. Biochem, 1997, 326: 693-700.
[71] Golovkin M, Reddy AS. An SC35-like protein and a novel serine/arginine-rich protein interact with Arabidopsis U1-70K protein [J]. Biol Chem. 1999, 274(51): 36428-36438.
[72] Tang Z, Mandel LL. The kic1 kinase of schizosaccharomyces pombe is a CLK/STY orthologue that regulates cell-cell separation [J]. Exp Cell Res. 2003, 283(1): 101-115.
[73] Labourier E, Rossi F. Interaction between the N-terminal domain of human DNA topoisomerase I and the arginine-serine domain of its substrate determines phosphorylation of ASF/SF2 splicing factor [J]. Nucleic Acids Res. 1998, 26(12): 2955-2962.
[74] Ross F, Labourier E. Specifc phosphorylation of SR proteins by mammalian DNA topoisomerase I [J]. Nature, 1996, 381: 80-82.
[75] Okamoto Y, Onogi H. cdc2 kinase-mediated phosphorylation of splicing factor SF2/ASF [J]. BBRC, 1998, 249, 872-878.
[76] Siebel CW, Feng L. Conservation in budding yeast of a kinase specific for SR splicing factors [J]. PNAS, 1999, 96(10): 5440-5445.
[77] Moore BW, Perez VJ. Specific acidic proteins of the nervous system [M]. Carlson FD. Physiological and Biochemical Aspects of Nervous Integration [C]. Woods Hole. MA: Prentice Hall, 1967, 343-359.
[78] Affe MB. How do 14-3-3 proteins work?-Gatekeeper phosphorylation and the molecular anvil hypothesis [J]. FEBS letters,2002, 513(1): 53-57.
[79] Gardino AK, Smerdon SJ, Yaffe MB. Structural determinants of 14-3-3 binding specificities and regulation of subcellular localization of 14-3-3-ligand complexes: a comparison of the X-ray crystal structures of all human 14-3-3 isoforms [J]. Semin Cancer Biol, 2006, 16(3): 173-182.
[80] DeLille JM, Sehnke PC, Ferl RJ. The Arabidopsis 14-3-3 family of signaling regulators [J]. Plant Physiol,2001, 126(1):35-38.
[81] Aitken A. 14-3-3 proteins: a historic overview [J]. Semin Cancer Biol, 2006, 16(3): 162-172.
[82] Xiao B, Smerdon SJ, Jones DH, et al. Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways [J]. Nature, 1995, 376(6536): 188-191.
[83] Liu D, Bienkowska J, Petosa C, et al. Crystal structure of the zeta isoform of the 14-3-3 protein [J]. Nature, 1995, 376(6536): 191-194.
[84] Rittinger K, Budman J, Xu J, et al. Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding [J]. Mol Cell ,1999,4: 153-166.
[85] Pozuelo Rubio M, Geraghty KM, Wong BH, et al. 14-3-3-affinity purification of over 200 human phosphoproteins reveals new links to regulation of cellular metabolism, proliferation and trafficking [J]. Biochem J. 2004, 379: 395-408.
[86] Aitken A, Baxter H, Dubois T, et al. Specificity of 14-3-3 isoform dimer interactions and phosphorylation [J]. Biochem Soc Trans, 2002, 30(4): 351-360.
[87] Fu H, Subramanian RR, Masters SC. 14-3-3 proteins: structure, function, and regulation [J]. Annu Rev Pharmacol Toxicol. 2000, 40: 617-647.
[88] Mhawech P. 14-3-3 proteins-an update [J]. Cell Res, 2005, 15(4): 228-236.
[89] Deborah K. Morrison. The 14-3-3 proteins: integrators of diverse signaling cues that impact cell fate and cancer development [J]. Trends in Cell Biology, 2008,19 (1):16-23.
[90] Aitken A. Functional specificity in 14-3-3 isoform interactions through dimer formation and phosphorylation. Chromosome location of mammalian isoforms and variants [J]. Plant Mol Biol,2002, 50(6): 993-1010.
[91] Yongsheng Shi, James L. Manley. A Complex Signaling Pathway Regulates SRp38 Phosphorylation and Pre-mRNA Splicing in Response to Heat Shock [J]. Mol Cell. 2007, 28: 79–90.
[92] Liu SD, Zhang JH, Xing M. The Characteristics of PSCL32.5 Protein from Physarum polycephalum and the Variation of the Content Through Cell Cycle [J]. Acta Genetica Sinica. 2004, 31(3): 305-310.
[93]张建华:多头绒泡菌SRPK类似蛋白cDNA的克隆[D].深圳大学硕士论文,2004.
[94]欧阳秋玲:应用酵母双杂交技术筛选多头绒泡菌PSRPK相关蛋白基因[D].深圳大学硕士论文,2006.
[95] Ellis JD, LIères D, Denegri M, et al. Spatial mapping of splicing factor complexes involved in exon and intron definition [J]. J Cell Biol, 2008,181(6):921-934.
[96]李明华.多头绒泡菌14-3-3蛋白基因克隆及其相关蛋白筛选[D].深圳大学硕士论文, 2008.
[97] Daniel J W, Baldwin H H. Methods of culture of plasmodial myxomycetes[M]. Methods in Cell Physiol[C]. New York: Academic Press. 1964. 9-14
[98]欧阳秋玲,刘士德,张建华等.应用酵母双杂交技术筛选多头绒泡菌PSRPK相关蛋白基因[J].深圳大学学报, 2006, 23(3): 222-229.
[99]郑东.荧光共振能盆转移显微术及其新进展[J].新技术应用, 2003, 1: 43-46.
[100] Forster T. Intramolecular energy migration and fluorescence [J]. Ann Phys, 1948, 2: 55.
[101] Ma CT, Velazquez-Dones A, Hagopian JC, et al.. Ordered multi-site phosphorylation of the splicing factor ASF/SF2 by SRPK1 [J]. J Mol Biol. 2008, 376: 55-68.
[102] Peter J Shepard, Klemens J Hertel. The SR protein family [J]. Genome Biology 2009, 10:242.1-242.7
[103] Xu YZ, Newnham CM, Kameoka S, et al. Prp5 bridges U1 and U2 snRNPs and enables stable U2 snRNP association with intron RNA [J]. EMBO J, 2004, 23: 376-385.
[104]邵伟,樊玉杰,徐永镇. SR蛋白家族在RNA剪接中的调控作用[J].生命科学,2010, 22(7):710-716.
[105] Escobar AJ, Arenas AF, Gomez-Marin JE: Molecular evolution of serine/arginine splicing factors family (SR) by positive selection [J]. In Silico Biol, 2006, 6:347-350.
[106]康康.多头绒泡菌SR蛋白激酶SRPK的磷酸化性质研究[D].深圳大学硕士论文, 2007.
[107] Gourisankar Ghosh, Joseph A. Adams. Phosphorylation mechanism and structure of serine-arginine protein kinases [J]. FEBS Journal ,2011, 278: 587–597.
[108] Ngo JC, Chakrabarti S, Ding JH, et al. Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 ini regulalted by a Docking motif in ASF/SF2 [J]. Molecular Cell. 2005, 20: 77-89.
[109] Arnold K, Bordoli L, Kopp J, Schwede T. The SWISS-MODEL Workspace: A web-based environment for protein structure homology modelling [J]. Bioinformatics. 2006, 22: 195-201.
[110] Hanks SK. Genomic analysis of the eukaryotic protein kinase superfamily: a perspective [J]. Genome Biol. 2003, 4(5):111-115.
[111] Ali GS,Reddy AS. ATP, phosphorylation and transcription regulate the mobility of plant splicing factors [J]. J Cell Sci,2006,119 (17):3527-3538.
[112] Kruhlak MJ, Lever MA, Fisehle W, et al. Reduced mobility of the alternate splicing factor (ASF) through the nucleoplasm and steady state specle compartments [J]. J Cell Biol,2000, 150:41-51.
[113] Phair RD, Misteli T. High mobility of proteins in the mammalian cell nueleus [J]. Nature,2000,404:604-609.
[114] Tillemans V, Leponce I, Rausin G, et al. Insights into nuclear organization in plants as revealed by the dynamic distribution of Arabidopsis SR splicing factors [J]. Plant Cell, 2006, 18:3218-3234.
[2] Krainer AR, Conway GC, Kozak D. The essential pre-mRNA splicing factor SF2 influences 5' splice site selection by activating proximal sites [J]. Cell, 1990, 62(1): 35-42.
[3] Ge H, Manley JL. A protein factor, ASF, controls cell-specific alternative splicing of SV40 early pre-mRNA in vitro [J]. Cell, 1990, 62(1): 25-34.
[4] Zuo P, Manley JL. Functional domains of the human splicing factor ASF/SF2 [J]. EMBO J, 1993, 12(12): 4727-4737.
[5] Fu XD, Maniatis T. Factor required for mammalian spliceosome assembly is localized to discrete regions in the nucleus [J]. Nature,1990, 343(6257): 437-441.
[6] Fu XD, Maniatis T. Isolation of a complementary DNA that encodes the mammalian splicing factor SC35 [J]. Science, 1992, 256(5056): 535-538.
[7] Roth MB, Murphy C, Gall JG. A monoclonal antibody that recognizes a phosphorylated epitope stains lampbrush chromosome loops and small granules in the amphibian germinal vesicle [J]. J Cell Biol, 1990, 111: 2217-2223.
[8] Mayeda A, Zahler AM, Krainer AR, Roth MB. Two members of a conserved family of nuclear phosphoproteins are involved in pre-mRNA splicing [J]. Proc Natl Acad Sci USA, 1992, 89(4): 1301-1304.
[9] Roth MB, Zahler AM, Stolk JA. A conserved family of nuclear phosphoproteins localized to sites of polymerase II transcription [J]. J Cell Biol, 1991, 115(3): 587-596.
[10] Zahler AM, Lane WS, Stolk JA, Roth MB. SR proteins: a conserved family of pre-mRNA splicing factors [J]. Genes Dev, 1992, 6(5): 837-847.
[11] Graveley BR. Sorting out the complexity of SR protein functions [J]. RNA, 2000, 6: 1197-1211.
[12] Lazar G, Schaal T, Maniatis T, Goodman HM. Identification of a plant serine-arginine-rich protein similar to the mammalian splicing factor SF2/ASF [J]. Proc Natl Acad Sci USA,1995, 92(17): 7672-7676.
[13] Lopato S, Mayeda A, Krainer AR, Barta A. Pre-mRNA splicing in plants: characterization of Ser/Arg splicing factors [J]. Proc Natl Acad Sci USA, 1996, 93(7): 3074-3079.
[14] Lorkovic ZJ, Barta A. Genome analysis: RNA recognition motif (RRM) and K homology (KH) domain RNA-binding proteins from the flowering plant Arabidopsis thaliana [J]. Nucleic Acids Res, 2002, 30, 623–635.
[15] Jennifer C. LONG, Javier F. CACERES. The SR protein family of splicing factors: master regulators of gene expression [J]. Biochem. J,2009,417:15–27.
[16] Spector DL, Fu XD, Maniatis T. Associations between distinct pre-mRNA splicing components and the cell nucleus [J]. EMBO J. 1991, 10(11): 3467-3481.
[17] Ali GS, Golovkin M, Reddy AS. Nuclear localization and in vivo dynamics of a plant-specific serine/arginine-rich protein [J]. Plant J. 2003, 36(6): 883-893.
[18] Graveley BR, Hertel KJ. SR proteins [M]. In Encyclopedia of Life Sciences. Chichester: John Wiley & Sons; 2005. doi:10.1038/npg.els.0005039.
[19] Liu HX, Zhang M, and Krainer AR. Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins [J]. Gene & Dev. 1998, 12: 1998-2012.
[20] Zuo P, Manley JL. The human splicing factor ASF/SF2 can specifically recognize pre-mRNA 5 splice sites [J]. Proc Natl Acad Sci USA.1994, 91: 3363-3367.
[21] Jamison SF, Pasman Z, Wang J, Will C, Luhrmann R, Manley JL, Garcia-Blanco MA. U1 snRNP-ASF/SF2 interaction and 5' splice site recognition: characterization of required elements [J]. Nucleic Acids Res, 1995, 23(16): 3260-3267.
[22] Liu HX, Chew SL, Cartegni L, Krainer AR. Exonic splicing enhancer motif recognized by human SC35 under splicing conditions [J]. Mol Biol Cell, 2000, 20: 1063-1071.
[23] Forment J, Naranjo MA, Roldan M, Serrano R, Vicente O. Expression of Arabidopsis SR-like splicing proteins confers salt tolerance to yeast and transgenic plants [J]. Plant J, 2002, 30(5): 511-519.
[24] Cáceres JF, Screaton GR, Krainer AR. A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm [J]. Genes Dev, 1998, 12:55-66.
[25] Huang Y, Steitz JA. Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA [J]. Mol Cell, 2001, 7: 899-905.
[26] Lee MS, Henry M, Silver PA. A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export [J]. Genes Dev, 1996, 10:1233-1246.
[27] Gilbert W, Siebel CW, Guthrie C. Phosphorylation by Sky1p promotes Npl3p shuttling and mRNA dissociation [J]. RNA, 2001, 7:302-313.
[28] Blencowe BJ, Nickerson JA, Issner R, et al. Association of nuclear matrix antigens with exon-containing splicing complexes [J]. J Cell Biol, 1994, 127:593-607.
[29] Le Hir H, Moore MJ, Maquat LE. Pre-mRNA splicing alters mRNP composition: evidence for stable association of proteins at exon-exon junctions [J]. Genes Dev, 2000, 14:1098-1108.
[30] Hautbergue GM, Hung ML, Golovanov AP, et al. Mutually exclusive interactions drive handover of mRNA from export adaptors to TAP [J]. Proc Natl Acad Sci USA, 2008, 105:5154-5159.
[31] Karni R, de Stanchina E, Lowe SW, et al. The gene encoding the splicing factor SF2/ASF is a proto-oncogene [J]. Nat Struct Mol Biol, 2007, 14:185-193.
[32] Sanford JR, Gray NK, Beckmann K, Caceres JF. A novel role for shuttling SR proteins in mRNA translation [J]. Genes Dev, 2004, 18:755-768.
[33] Michlewski G, Sanford JR, Caceres JF. The splicing factor SF2/ASF regulates translation initiation by enhancing phosphorylation of 4E-BP1 [J]. Mol Cell, 2008, 3:179-189.
[34] Cao WH, Jamison SF, Garrcia-Blanco MA. Both phosphorylation and dephosphorylation of ASF/SF2 are required for pre-mRNA splicing in vitro [J]. RNA, 1997, 3:1456-1467.
[35] Misteli T, Caceres JF, Clement JQ, Krainer AR, Wilkinson MF, and Spector DL. Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo [J]. J Cell Biol. 1998, 143(2): 297-307.
[36] Xiao SH, Manley JL. Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2 [J]. EMBO J. 1998, 17: 6359-6367.
[37] Koizumi J, Okamoto Y, Onogi H, Mayeda A, Krainer AR., and Hagiwara M. The subcellular localization of SF2/ASF is regulated by direct interaction with SR protein kinases (SRPKs) [J]. J. Biol. Chem. 1999, 274(16): 11125-11131.
[38] Gui JF, Lane WS. A serine kinase regulates intracellular localization of splicing factors in the cell cycle [J]. Nature, 1994, 369(6482): 678-682.
[39] Misteli T, Caceres JF, Clement JQ, et al. Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo [J]. J Cell Biol, 1998, 143(2): 297-307.
[40] Gui JF, Tronchere H. Purification and characterization of a kinase specific for the serine- and arginine-rich pre-mRNA splicing factors [J]. PNAS, 1994, 91(23): 10824-10828.
[41] Wang HY, Lin W. SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells [J]. Cell Biol, 1998, 140(4): 737-750.
[42] Colwill K, Feng LL, Yeakley JM, et al. SRPK1 and Clk/Sty protein kinases show distinct substrate specificities for serine/arginine-rich splicing factors [J]. Biol Chem, 1996, 271(40): 24569-24575.
[43] Tillemans V. Leponce I, Rausin G, et al. Insights into nuclear organization in plants as revealed by the dynamic distribution of Arabidopsis SR splicing factors [J]. Plant Cell ,2006, 18: 3218-3234.
[44] Caceres JF, Screaton GR, Krainer AR. A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm [J]. Genes Dev. 1998, 12:55-56.
[45] Yang L, Lisa J. Embree, Schickwann Tsai, et al. Oncoprotein TLS Interacts with Serine-Arginine Proteins Involved in RNA Splicing [J]. J Biol Chem, 1998, 273: 27761 -27764.48
[46] Aubol BE, Chakrabarti S, Ngo J, et al. Processive phosphorylation of alternative splicing factor/splicing factor 2 [J]. Proc Natl Acad Sci USA. 2003, 100: 12601-12606.
[47] Adolfo VD, Hagopian JC, Ma CT, et al.. Mass spectrometric and kinetic analysis of ASF/SF2 phosphorylation by SRPK1 and Clk/Sty [J]. J Biol Chem. 2005, 280(50): 41761-41768.
[48] Ngo JC, Chakrabarti S, Ding JH, et al. Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 ini regulalted by a Docking motif in ASF/SF2 [J]. Molecular Cell, 2005, 20: 77-89.
[49] Clinton JM, Chansky HA, Odell DD, et al. Characterization and expression of the human gene encoding two translocation liposarcoma protein-associated serine-arginine (TASR) [J] proteins.Gene, 2002, 284: 141-147.
[50] Komatsu M, Kominami E, Arahata K, et al. Cloning and characterization of two neural-salient serine/arginine-rich (NSSR) proteins involved in the regulation of alternativesplicing in neurones [J]. Genes Cells, 1999, 4:593-606.
[51] Woppmann A, Will CL, Kornstadt U, et al. Identification of an snRNP-associated kinase activity that phosphorylates arginine/serine rich domains typical of splicing factors [J]. Nucleic Acids Res, 1993, 21(12): 2815-2822.
[52] Thomas Giannakouros, Eleni Nikolakaki, Ilias Mylonis, et al. Serine-arginine protein kinases: a small protein kinase family with a large cellular presence [J]. FEBS J, 2011, 278: 570–586.
[53] Misteli T, Spector DL. Serine/threonine phosphatase 1 modulates the subnuclear distribution of pre-mRNA splicing factors [J]. Mol Biol Cell, 1996, 7(10): 1559-1572.
[54] Sacco-Bubulya P, Spector DL. Disassembly of interchromatin granule clusters alters the coordination of transcription and pre-mRNA splicing [J]. Cell Biol, 2002, 156(3): 425-436.
[55] Prasanth KV, Sacco-Bubulya PA. Prasanth SG, Spector DL. Sequential entry of components of the gene expression machinery into daughter nuclei [J]. Mol Biol Cell, 2003, 14(3):1043-1057.
[56] Fang Y, Hearn S, Spector DL. Tissue-specific expression and dynamic organization of SR splicing factors in Arabidopsis [J]. Mol Biol Cell. 2004, 15(6): 2664-2673.
[57] Nikolakaki E, Kohen R, Hartmann AM, et al. Cloning and characterization of an alternatively spliced form of SR protein kinase 1 that interacts specifically with scaffold attachment factor-B [J]. J Biol Chem, 2001, 276(43): 40175-40182.
[58] Papoutsopoulou S, Nikolakaki E, Giannakouros T. SRPK1 and LBR protein kinases show identical substrate specificities [J]. BBRC,1999, 255(3): 602-607.
[59] Papoutsopoulou S, Nikolakaki E, Chalepakis G, et al. SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1 [J]. Nucleic Acids Res. 1999, 27(14): 2972-2980.
[60] Daub H, Blencke S, Habenberger P, et al. Identification of SRPK1 and SRPK2 as the major cellular protein kinases phosphorylating hepatitis B virus core protein [J]. Virol, 2001, 76(16): 8124-8137.
[61] Lee CG, Hague LK, Li H, Donnelly R. Identification of toposome, a novel multisubunit complex containing topoisomerase II alpha [J]. Cell Cycle, 2004, 3(5): 638-647.
[62] Thomas Giannakouros, Eleni Nikolakaki, Ilias Mylonis, et al. Serine-arginine proteinkinases: a small protein kinase family with a large cellular presence [J]. FEBS Journal, 2011,278:570–586
[63] Hanks SK, Hunter T. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification [J]. FASEB,1995, 9: 576-596.
[64] Kuroyanagi N, Onogi H. Novel SR-protein-specific kinase, SRPK2, disassembles nuclear speckles [J]. BBRC, 1998, 242(2): 357-364.
[65] Tang Z, Yanagida M. Fission yeast mitotic regulator Dsk1 is an SR protein-specific kinase [J]. Biol Chem, 1998, 273(10): 5963-5969.
[66] Siebel CW, Feng L. Conservation in budding yeast of a kinase specific for SR splicing factors [J]. PNAS, 1999, 96(10): 5440-5445.
[67] Kuroyanagi H, Kimura T. SPK-1, a C. elegans SR protein kinase homologue, is essential for embryogenesis and required for germline development [J]. Mech Dev, 2000, 99(1-2): 51-64.
[68] Portal D, Lobo GS. Trypanosoma cruzi TcSRPK, the first protozoan member of the SRPK family, is biochemically and functionally conserved with metazoan SR protein-specific kinases [J]. Mol Biochem Parasitol, 2003, 127(1): 9-21.
[69] Colwill K, Pawson T. The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution [J]. EMBO J, 1996, 15, 265-275.
[70] Nayler O, Stamm S. Characterization and comparison of four serine- and arginine-rich (SR) protein kinases [J]. Biochem, 1997, 326: 693-700.
[71] Golovkin M, Reddy AS. An SC35-like protein and a novel serine/arginine-rich protein interact with Arabidopsis U1-70K protein [J]. Biol Chem. 1999, 274(51): 36428-36438.
[72] Tang Z, Mandel LL. The kic1 kinase of schizosaccharomyces pombe is a CLK/STY orthologue that regulates cell-cell separation [J]. Exp Cell Res. 2003, 283(1): 101-115.
[73] Labourier E, Rossi F. Interaction between the N-terminal domain of human DNA topoisomerase I and the arginine-serine domain of its substrate determines phosphorylation of ASF/SF2 splicing factor [J]. Nucleic Acids Res. 1998, 26(12): 2955-2962.
[74] Ross F, Labourier E. Specifc phosphorylation of SR proteins by mammalian DNA topoisomerase I [J]. Nature, 1996, 381: 80-82.
[75] Okamoto Y, Onogi H. cdc2 kinase-mediated phosphorylation of splicing factor SF2/ASF [J]. BBRC, 1998, 249, 872-878.
[76] Siebel CW, Feng L. Conservation in budding yeast of a kinase specific for SR splicing factors [J]. PNAS, 1999, 96(10): 5440-5445.
[77] Moore BW, Perez VJ. Specific acidic proteins of the nervous system [M]. Carlson FD. Physiological and Biochemical Aspects of Nervous Integration [C]. Woods Hole. MA: Prentice Hall, 1967, 343-359.
[78] Affe MB. How do 14-3-3 proteins work?-Gatekeeper phosphorylation and the molecular anvil hypothesis [J]. FEBS letters,2002, 513(1): 53-57.
[79] Gardino AK, Smerdon SJ, Yaffe MB. Structural determinants of 14-3-3 binding specificities and regulation of subcellular localization of 14-3-3-ligand complexes: a comparison of the X-ray crystal structures of all human 14-3-3 isoforms [J]. Semin Cancer Biol, 2006, 16(3): 173-182.
[80] DeLille JM, Sehnke PC, Ferl RJ. The Arabidopsis 14-3-3 family of signaling regulators [J]. Plant Physiol,2001, 126(1):35-38.
[81] Aitken A. 14-3-3 proteins: a historic overview [J]. Semin Cancer Biol, 2006, 16(3): 162-172.
[82] Xiao B, Smerdon SJ, Jones DH, et al. Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways [J]. Nature, 1995, 376(6536): 188-191.
[83] Liu D, Bienkowska J, Petosa C, et al. Crystal structure of the zeta isoform of the 14-3-3 protein [J]. Nature, 1995, 376(6536): 191-194.
[84] Rittinger K, Budman J, Xu J, et al. Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding [J]. Mol Cell ,1999,4: 153-166.
[85] Pozuelo Rubio M, Geraghty KM, Wong BH, et al. 14-3-3-affinity purification of over 200 human phosphoproteins reveals new links to regulation of cellular metabolism, proliferation and trafficking [J]. Biochem J. 2004, 379: 395-408.
[86] Aitken A, Baxter H, Dubois T, et al. Specificity of 14-3-3 isoform dimer interactions and phosphorylation [J]. Biochem Soc Trans, 2002, 30(4): 351-360.
[87] Fu H, Subramanian RR, Masters SC. 14-3-3 proteins: structure, function, and regulation [J]. Annu Rev Pharmacol Toxicol. 2000, 40: 617-647.
[88] Mhawech P. 14-3-3 proteins-an update [J]. Cell Res, 2005, 15(4): 228-236.
[89] Deborah K. Morrison. The 14-3-3 proteins: integrators of diverse signaling cues that impact cell fate and cancer development [J]. Trends in Cell Biology, 2008,19 (1):16-23.
[90] Aitken A. Functional specificity in 14-3-3 isoform interactions through dimer formation and phosphorylation. Chromosome location of mammalian isoforms and variants [J]. Plant Mol Biol,2002, 50(6): 993-1010.
[91] Yongsheng Shi, James L. Manley. A Complex Signaling Pathway Regulates SRp38 Phosphorylation and Pre-mRNA Splicing in Response to Heat Shock [J]. Mol Cell. 2007, 28: 79–90.
[92] Liu SD, Zhang JH, Xing M. The Characteristics of PSCL32.5 Protein from Physarum polycephalum and the Variation of the Content Through Cell Cycle [J]. Acta Genetica Sinica. 2004, 31(3): 305-310.
[93]张建华:多头绒泡菌SRPK类似蛋白cDNA的克隆[D].深圳大学硕士论文,2004.
[94]欧阳秋玲:应用酵母双杂交技术筛选多头绒泡菌PSRPK相关蛋白基因[D].深圳大学硕士论文,2006.
[95] Ellis JD, LIères D, Denegri M, et al. Spatial mapping of splicing factor complexes involved in exon and intron definition [J]. J Cell Biol, 2008,181(6):921-934.
[96]李明华.多头绒泡菌14-3-3蛋白基因克隆及其相关蛋白筛选[D].深圳大学硕士论文, 2008.
[97] Daniel J W, Baldwin H H. Methods of culture of plasmodial myxomycetes[M]. Methods in Cell Physiol[C]. New York: Academic Press. 1964. 9-14
[98]欧阳秋玲,刘士德,张建华等.应用酵母双杂交技术筛选多头绒泡菌PSRPK相关蛋白基因[J].深圳大学学报, 2006, 23(3): 222-229.
[99]郑东.荧光共振能盆转移显微术及其新进展[J].新技术应用, 2003, 1: 43-46.
[100] Forster T. Intramolecular energy migration and fluorescence [J]. Ann Phys, 1948, 2: 55.
[101] Ma CT, Velazquez-Dones A, Hagopian JC, et al.. Ordered multi-site phosphorylation of the splicing factor ASF/SF2 by SRPK1 [J]. J Mol Biol. 2008, 376: 55-68.
[102] Peter J Shepard, Klemens J Hertel. The SR protein family [J]. Genome Biology 2009, 10:242.1-242.7
[103] Xu YZ, Newnham CM, Kameoka S, et al. Prp5 bridges U1 and U2 snRNPs and enables stable U2 snRNP association with intron RNA [J]. EMBO J, 2004, 23: 376-385.
[104]邵伟,樊玉杰,徐永镇. SR蛋白家族在RNA剪接中的调控作用[J].生命科学,2010, 22(7):710-716.
[105] Escobar AJ, Arenas AF, Gomez-Marin JE: Molecular evolution of serine/arginine splicing factors family (SR) by positive selection [J]. In Silico Biol, 2006, 6:347-350.
[106]康康.多头绒泡菌SR蛋白激酶SRPK的磷酸化性质研究[D].深圳大学硕士论文, 2007.
[107] Gourisankar Ghosh, Joseph A. Adams. Phosphorylation mechanism and structure of serine-arginine protein kinases [J]. FEBS Journal ,2011, 278: 587–597.
[108] Ngo JC, Chakrabarti S, Ding JH, et al. Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 ini regulalted by a Docking motif in ASF/SF2 [J]. Molecular Cell. 2005, 20: 77-89.
[109] Arnold K, Bordoli L, Kopp J, Schwede T. The SWISS-MODEL Workspace: A web-based environment for protein structure homology modelling [J]. Bioinformatics. 2006, 22: 195-201.
[110] Hanks SK. Genomic analysis of the eukaryotic protein kinase superfamily: a perspective [J]. Genome Biol. 2003, 4(5):111-115.
[111] Ali GS,Reddy AS. ATP, phosphorylation and transcription regulate the mobility of plant splicing factors [J]. J Cell Sci,2006,119 (17):3527-3538.
[112] Kruhlak MJ, Lever MA, Fisehle W, et al. Reduced mobility of the alternate splicing factor (ASF) through the nucleoplasm and steady state specle compartments [J]. J Cell Biol,2000, 150:41-51.
[113] Phair RD, Misteli T. High mobility of proteins in the mammalian cell nueleus [J]. Nature,2000,404:604-609.
[114] Tillemans V, Leponce I, Rausin G, et al. Insights into nuclear organization in plants as revealed by the dynamic distribution of Arabidopsis SR splicing factors [J]. Plant Cell, 2006, 18:3218-3234.