Trihydrophobin 1与PAK1的相互作用及其生物学功能的研究
|
摘要
Rac1/Cdc42的效应子PAK被不同的信号级联反应活化,包括酪氨酸激酶受体和integrins受体,并且它也调控着大量的生物学过程,如细胞增殖和细胞迁移等。PAK的活化曾被报道对RAF-MEK-MAPK信号通路的最大活化是必须的,可能是因为PAK能够同时活化RAF和MEK的缘故。在本论文中,我们证实了起初被鉴定为A-RAF激酶特异负调节子的TH1在细胞中也和PAK1有相互作用。荧光共聚焦显微镜分析显示TH1和PAK1在细胞核和胞浆中都有共定位,这种现象和我们目前的结果相一致。GST pull-down和免疫共沉淀实验证实了TH1和PAK1能直接相互作用,并且选择性的结合到PAK1 C端的激酶域上。TH1和PAK1结合的能力随着PAK1的活化而增强。和PAK1的这种结合形式暗示了他们间的相互作用部分是被PAK1激酶活性所调控的。正如体外激酶活性分析和Western Blot检测所显示的,TH1抑制了PAK1激酶活性并且负调节了MAPK信号的传导。有趣的是,TH1在体内和体外都和MEK1/ERK结合,但并不直接抑制他们的激酶活性。此外,我们还观察到TH1定位于迁移细胞前沿的粘附斑和纤维伪足上,并且通过影响肌动蛋白和粘附动力学变化干扰了细胞的迁移。基于这些实验数据,我们提出了一个模型:TH1和PAK1相互作用,并通过MAPK通路的上游特异地限制了MAPK模块的活化,从而影响了细胞的迁移。
The Rac1/Cdc42 effector,p21-activated kinase,is activated by various signaling cascades,including receptor-tyrosine kinasesand integrins,and regulates a number of processes such as cell proliferation and motility.PAK activity has been shown to be required for maximal activation of the canonical RAF-MEK-MAPK signaling cascade,possibly because of PAK co-activation of RAF and MEK.Here we have shown that trihydrophobin 1(TH1),originally identified as a negative regulator of A-RAF kinase,also interacted with PAK1 in cultured cells.Confocal microscopy assay indicated that TH1 colocalized with PAK1 in both the cytoplasm and nucleus,which is consistent with our previous results.GST pull-down and coimmunoprecipitation experiments demonstrated that TH1 interacted directly with PAK1 and bound selectively to the carboxyl-terminal kinase domain of PAK1,and the ability of the binding was enhanced along with activation of PAK1.The binding pattern of PAK1 implies that this interaction was mediated in part by PAK1 kinase activity. As indicated by in vitro kinase activity assays and Western blot detections, TH1 inhibited PAK1 kinase activity and negatively regulated MAPK signal transduction.Interestingly,TH1 bound with MEK1/ERK in cells and in vitro without directly suppressing their kinase activity.Furthermore,we observed that TH1 localized to focal adhesions and filopodia in the leading edge of cells,where TH1 reduced cell migration through affecting actin and adhesion dynamics.Based on these observations,we propose a model in which TH1 interacts with PAK1 and specifically restricts the activation of MAPK modules through the upstream of the MAPK pathway,thereby influencing cell migration.
The Rac1/Cdc42 effector,p21-activated kinase,is activated by various signaling cascades,including receptor-tyrosine kinasesand integrins,and regulates a number of processes such as cell proliferation and motility.PAK activity has been shown to be required for maximal activation of the canonical RAF-MEK-MAPK signaling cascade,possibly because of PAK co-activation of RAF and MEK.Here we have shown that trihydrophobin 1(TH1),originally identified as a negative regulator of A-RAF kinase,also interacted with PAK1 in cultured cells.Confocal microscopy assay indicated that TH1 colocalized with PAK1 in both the cytoplasm and nucleus,which is consistent with our previous results.GST pull-down and coimmunoprecipitation experiments demonstrated that TH1 interacted directly with PAK1 and bound selectively to the carboxyl-terminal kinase domain of PAK1,and the ability of the binding was enhanced along with activation of PAK1.The binding pattern of PAK1 implies that this interaction was mediated in part by PAK1 kinase activity. As indicated by in vitro kinase activity assays and Western blot detections, TH1 inhibited PAK1 kinase activity and negatively regulated MAPK signal transduction.Interestingly,TH1 bound with MEK1/ERK in cells and in vitro without directly suppressing their kinase activity.Furthermore,we observed that TH1 localized to focal adhesions and filopodia in the leading edge of cells,where TH1 reduced cell migration through affecting actin and adhesion dynamics.Based on these observations,we propose a model in which TH1 interacts with PAK1 and specifically restricts the activation of MAPK modules through the upstream of the MAPK pathway,thereby influencing cell migration.
引文
[1] Manser, E., Leung, T., Salihuddin, H., Zhao, Z. S. & Lim, L. A brain serine/threonine protein kinase activated by Cdc42 and Racl. Nature 367,40-6 (1994).
[2] Knaus, U. G & Bokoch, G M. The p21Rac/Cdc42-activated kinases (PAKs). Int J Biochem Cell Biol 30, 857-62 (1998).
[3] Bokoch, G. M. Biology of the p21-activated kinases. Annu Rev Biochem 72, 743-81 (2003).
[4] Kumar, R. & Vadlamudi, R. K. Emerging functions of p21-activated kinases in human cancer cells. J Cell Physiol 193,133-44 (2002).
[5] Leberer, E., Thomas, D. Y. & Whiteway, M. Pheromone signalling and polarized morphogenesis in yeast. Curr Opin Genet Dev 7, 59-66 (1997).
[6] Jaffer, Z. M. & Chernoff, J. p21-activated kinases: three more join the Pak. Int J Biochem Cell Biol 34, 713-7 (2002).
[7] Dan, C, Nath, N., Liberto, M. & Minden, A. PAK5, a new brain-specific kinase, promotes neurite outgrowth in N1E-115 cells. Mol Cell Biol 22, 567-77 (2002).
[8] Parrini, M. C, Lei, M., Harrison, S. C. & Mayer, B. J. Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Racl. Mol Cell 9, 73-83 (2002).
[9] Chong, C., Tan, L., Lim, L. & Manser, E. The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity. J Biol Chem 276, 17347-53 (2001).
[10] Buchwald, G., Hostinova, E., Rudolph, M. G., Kraemer, A., Sickmann, A., Meyer, H. E., Scheffzek, K. & Wittinghofer, A. Conformational switch and role of phosphorylation in PAK activation. Mol Cell Biol 21, 5179-89 (2001).
[11] Dharmawardhane, S., Sanders, L. C., Martin, S. S., Daniels, R. H. & Bokoch, G. M. Localization of p21-activated kinase 1 (PAK1) to pinocytic vesicles and cortical actin structures in stimulated cells. J Cell Biol 138, 1265-78 (1997).
[12] Sells, M. A., Pfaff, A. & Chernoff, J. Temporal and spatial distribution of activated Pak1 in fibroblasts. J Cell Biol 151, 1449-58 (2000).
[13] Sells, M. A., Knaus, U. G., Bagrodia, S., Ambrose, D. M., Bokoch, G. M. & Chernoff, J. Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells. Curr Biol 7,202-10 (1997).
[14] Sells, M. A., Boyd, J. T. & Chernoff, J. p21 -activated kinase 1 (Pak1) regulates cell motility in mammalian fibroblasts. J Cell Biol 145, 837-49 (1999).
[15] Manser, E., Huang, H. Y., Loo, T. H., Chen, X. Q., Dong, J. M., Leung, T. & Lim, L. Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes. Mol Cell Biol 17, 1129-43 (1997).
[16] Frost, J. A., Khokhlatchev, A., Stippec, S., White, M. A. & Cobb, M. H. Differential effects of PAK1-activating mutations reveal activity-dependent and -independent effects on cytoskeletal regulation. J Biol Chem 273, 28191-8 (1998).
[17] Kiosses, W. B., Daniels, R. H., Otey, C, Bokoch, G M. & Schwartz, M. A. A role for p21-activated kinase in endothelial cell migration. J Cell Biol 147, 831-44(1999).
[18] Edwards, D. C., Sanders, L. C., Bokoch, G. M. & Gill, G. N. Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nat Cell Biol 1,253-9 (1999).
[19] Sanders, L. C., Matsumura, F., Bokoch, G. M. & de Lanerolle, P. Inhibition of myosin light chain kinase by p21-activated kinase. Science 283, 2083-5 (1999).
[20] Vadlamudi, R. K., Li, F., Adam, L., Nguyen, D., Ohta, Y., Stossel, T. P. & Kumar, R. Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1. Nat Cell Biol 4, 681-90 (2002).
[21] Wittmann, T., Bokoch, G. M. & Waterman-Storer, C. M. Regulation of leading edge microtubule and actin dynamics downstream of Racl. J Cell Biol 161, 845-51 (2003).
[22] Krueger, J. S., Keshamouni, V. G, Atanaskova, N. & Reddy, K. B. Temporal and quantitative regulation of mitogen-activated protein kinase (MAPK) modulates cell motility and invasion. Oncogene 20, 4209-18 (2001).
[23] Jo, M., Thomas, K. S., Somlyo, A. V., Somlyo, A. P. & Gonias, S. L. Cooperativity between the Ras-ERK and Rho-Rho kinase pathways in urokinase-type plasminogen activator-stimulated cell migration. J Biol Chem 277, 12479-85 (2002).
[24] Huang, C., Jacobson, K. & Schaller, M. D. MAP kinases and cell migration. J Cell Sci 117, 4619-28 (2004).
[25] Webb, D. J., Donais, K., Whitmore, L. A., Thomas, S. M., Turner, C. E., Parsons, J. T. & Horwitz, A. F. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol 6,154-61 (2004).
[26] Slack-Davis, J. K., Eblen, S. T., Zecevic, M., Boerner, S. A., Tarcsafalvi, A., Diaz, H. B., Marshall, M. S., Weber, M. J., Parsons, J. T. & Catling, A. D. PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation. J Cell Biol 162, 281-91 (2003).
[27] Jin, S., Zhuo, Y., Guo, W. & Field, J. p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association. J Biol Chem 280, 24698-705 (2005).
[28] Sundberg-Smith, L. J., Doherty, J. T., Mack, C. P. & Taylor, J. M. Adhesion stimulates direct PAK1/ERK2 association and leads to ERK-dependent PAK1 Thr212 phosphorylation. J Biol Chem 280, 2055-64 (2005).
[29] Chen, W, Chen, S., Yap, S. F. & Lim, L. The Caenorhabditis elegans p21-activated kinase (CePAK) colocalizes with CeRac1 and CDC42Ce at hypodermal cell boundaries during embryo elongation. J Biol Chem 271, 26362-8 (1996).
[30] Melzig, J., Rein, K. H., Schafer, U., Pfister, H., Jackie, H., Heisenberg, M. & Raabe, T. A protein related to p21-activated kinase (PAK) that is involved in neurogenesis in the Drosophila adult central nervous system. Curr Biol 8, 1223-6 (1998).
[31] Hing, H., Xiao, J., Harden, N., Lim, L. & Zipursky, S. L. Pak functions downstream of Dock to regulate photoreceptor axon guidance in Drosophila. Cell 97, 853-63 (1999).
[32] Chung, C. Y. & Firtel, R. A. PAKa, a putative PAK family member, is required for cytokinesis and the regulation of the cytoskeleton in Dictyostelium discoideum cells during chemotaxis. J Cell Biol 147, 559-76 (1999).
[33] Leberer, E., Ziegelbauer, K., Schmidt, A., Harcus, D., Dignard, D., Ash, J., Johnson, L. & Thomas, D. Y. Virulence and hyphal formation of Candida albicans require the Ste20p-like protein kinase CaCla4p. Curr Biol 7, 539-46 (1997).
[34] Burridge, K. Crosstalk between Rac and Rho. Science 283, 2028-9 (1999).
[35] Chrzanowska-Wodnicka, M. & Burridge, K. Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J Cell Biol 133, 1403-15 (1996).
[36] Waterman-Storer, C. M., Worthylake, R. A., Liu, B. P., Burridge, K. & Salmon, E. D. Microtubule growth activates Racl to promote lamellipodial protrusion in fibroblasts. Nat Cell Biol 1,45-50 (1999).
[37] Krendel, M., Zenke, F. T. & Bokoch, G M. Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton. Nat Cell Biol 4, 294-301 (2002).
[38] Banga, S. S., Yamamoto, A. H., Mason, J. M. & Boyd, J. B. Molecular cloning of mei-41, a gene that influences both somatic and germline chromosome metabolism of Drosophila melanogaster. Mol Gen Genet 246, 148-55 (1995).
[39] Haring, H. [Pathophysiology of insulin resistance]. Herz 20, 5-15 (1995).
[40] Bonthron, D. T., Hayward, B. E., Moran, V. & Strain, L. Characterization of TH1 and CTSZ, two non-imprinted genes downstream of GNAS1 in chromosome 20q13. Hum Genet 107, 165-75 (2000).
[41] Liu, W., Shen, X., Yang, Y, Yin, X., Xie, J., Yan, J., Jiang, J., Liu, W., Wang, H., Sun, M., Zheng, Y. & Gu, J. Trihydrophobin 1 is a new negative regulator of A-Raf kinase. J Biol Chem 279, 10167-75 (2004).
[42] Yang, Y, Liu, W., Zou, W., Wang, H., Zong, H., Jiang, J., Wang, Y. & Gu, J. Ubiquitin-dependent proteolysis of trihydrophobin 1 (TH1) by the human papilloma virus E6-associated protein (E6-AP). J Cell Biochem 101, 167-80 (2007).
[43] Yamaguchi, Y, Takagi, T., Wada, T., Yano, K., Furuya, A., Sugimoto, S., Hasegawa, J. & Handa, H. NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase Ⅱ elongation. Cell 97, 41-51 (1999).
[44] Narita, T., Yamaguchi, Y, Yano, K., Sugimoto, S., Chanarat, S., Wada, T., Kim, D. K., Hasegawa, J., Omori, M., Inukai, N., Endoh, M., Yamada, T. & Handa, H. Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex. Mol Cell Biol 23, 1863-73(2003).
[45] Wu, C. H., Yamaguchi, Y, Benjamin, L. R., Horvat-Gordon, M., Washinsky, J., Enerly, E., Larsson, J., Lambertsson, A., Handa, H. & Gilmour, D. NELF and DSIF cause promoter proximal pausing on the hsp70 promoter in Drosophila. Genes Dev 17, 1402-14(2003).
[46] Aiyar, S. E., Sun, J. L., Blair, A. L., Moskaluk, C. A., Lu, Y. Z., Ye, Q. N., Yamaguchi, Y, Mukherjee, A., Ren, D. M., Handa, H. & Li, R. Attenuation of estrogen receptor alpha-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor. Genes Dev 18, 2134-46 (2004).
[47] Alahari, S. K., Reddig, P. J. & Juliano, R. L. The integrin-binding protein Nischarin regulates cell migration by inhibiting PAK. Embo J 23, 2777-88 (2004).
[48] Lei, M., Robinson, M. A. & Harrison, S. C. The active conformation of the PAK1 kinase domain. Structure 13, 769-78 (2005).
[49] Lei, M., Lu, W., Meng, W., Parrini, M. C., Eck, M. J., Mayer, B. J. & Harrison, S. C. Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell 102, 387-97 (2000).
[50] Guo, D., Tan, Y. C., Wang, D., Madhusoodanan, K. S., Zheng, Y., Maack, T., Zhang, J. J. & Huang, X. Y. A Rac-cGMP signaling pathway. Cell 128, 341-55 (2007).
[51] Fincham, V. J., James, M., Frame, M. C. & Winder, S. J. Active ERK/MAP kinase is targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src. Embo J 19, 2911-23 (2000).
[52] Dharmawardhane, S., Brownson, D., Lennartz, M. & Bokoch, G. M. Localization of p21-activated kinase 1 (PAK1) to pseudopodia, membrane ruffles, and phagocytic cups in activated human neutrophils. J Leukoc Biol 66, 521-7(1999).
[53] Koestler, S. A., Auinger, S., Vinzenz, M, Rottner, K. & Small, J. V. Differentially oriented populations of actin filaments generated in lamellipodia collaborate in pushing and pausing at the cell front. Nat Cell Biol 10, 306-13 (2008).
[54] Nemethova, M., Auinger, S. & Small, J. V. Building the actin cytoskeleton: filopodia contribute to the construction of contractile bundles in the lamella. J Cell Biol 180, 1233-44 (2008).
[55] Serrels, B., Serrels, A., Brunton, V. G., Holt, M., McLean, G. W., Gray, C. H., Jones, G.E.& Frame, M. C. Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex. Nat Cell Biol 9, 1046-56 (2007).
[56] Ridley, A. J., Schwartz, M. A., Burridge, K., Firtel, R. A., Ginsberg, M. H., Borisy, G., Parsons, J. T. & Horwitz, A. R. Cell migration: integrating signals from front to back. Science 302,1704-9 (2003).
[57] Rayala, S. K., Talukder, A. H., Balasenthil, S., Tharakan, R., Barnes, C. J., Wang, R. A., Aldaz, M., Khan, S. & Kumar, R. P21-activated kinase 1 regulation of estrogen receptor-alpha activation involves serine 305 activation linked with serine 118 phosphorylation. Cancer Res 66,1694-701 (2006).
[58] Schrantz, N., da Silva Correia, J., Fowler, B., Ge, Q., Sun, Z. & Bokoch, G M. Mechanism of p21-activated kinase 6-mediated inhibition of androgen receptor signaling. J Biol Chem 279,1922-31 (2004).
[59] Lee, S. R., Ramos, S. M., Ko, A., Masiello, D., Swanson, K. D., Lu, M. L. & Balk, S. P. AR and ER interaction with a p21-activated kinase (PAK6). Mol Endocrinol 16, 85-99 (2002).
[60] Howe, A. K. & Juliano, R. L. Regulation of anchorage-dependent signal transduction by protein kinase A and p21-activated kinase. Nat Cell Biol 2, 593-600 (2000).
[61] Koh, C. G., Tan, E. J., Manser, E. & Lim, L. The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family. Curr Biol 12, 317-21 (2002).
[62] Zang, M., Hayne, C. & Luo, Z. Interaction between active Pakl and Raf-1 is necessary for phosphorylation and activation of Raf-1. J Biol Chem 277, 4395-405 (2002).
[63] King, B. H., Cromwell, H. C., Lee, H. T., Behrstock, S. P., Schmanke, T. & Maidment, N. T. Dopaminergic and glutamatergic interactions in the expression of self-injurious behavior. Dev Neurosci 20,180-7 (1998).
[64] Frost, J. A., Steen, H., Shapiro, P., Lewis, T., Ahn, N., Shaw, P. E. & Cobb, M. H. Cross-cascade activation of ERKs and ternary complex factors by Rho family proteins. Embo J 16, 6426-38 (1997).
[65] Kiosses, W. B., Shattil, S. J., Pampori, N. & Schwartz, M. A. Rac recruits high-affinity integrin alphavbeta3 to lamellipodia in endothelial cell migration. Nat Cell Biol 3, 316-20 (2001).
[66] Gabarra-Niecko, V., Schaller, M. D. & Dunty, J. M. FAK regulates biological processes important for the pathogenesis of cancer. Cancer Metastasis Rev 22, 359-74 (2003).
[67] Katz, M., Amit, I., Cirri, A., Shay, T., Carvalho, S., Lavi, S., Milanezi, F., Lyass, L., Amariglio, N., Jacob-Hirsch, J., Ben-Chetrit, N., Tarcic, G., Lindzen, M., Avraham, R., Liao, Y. C., Trusk, P., Lyass, A., Rechavi, G., Spector, N. L., Lo, S. H., Schmitt, F., Bacus, S. S. & Yarden, Y. A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration. Nat Cell Biol 9, 961-9 (2007).
[68] Geiger, B., Spatz, J. P. & Bershadsky, A. D. Environmental sensing through focal adhesions. Nat Rev Mol Cell Biol 10,21-33 (2009).
[69] Geiger, B., Bershadsky, A., Pankov, R. & Yamada, K. M. Transmembrane crosstalk between the extracellular matrix-cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2, 793-805 (2001).
[70] Emsley, J., Knight, C. G., Farndale, R. W., Barnes, M. J. & Liddington, R. C. Structural basis of collagen recognition by integrin alpha2betal. Cell 101, 47-56 (2000).
[71] Kim, M., Carman, C. V. & Springer, T. A. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 301, 1720-5 (2003).
[72] Huttenlocher, A., Ginsberg, M. H. & Horwitz, A. F. Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity. J Cell Biol 134,1551-62 (1996).
[73] Palecek, S. P., Loftus, J. C., Ginsberg, M. H., Lauffenburger, D. A. & Horwitz, A. F. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature 385, 537-40 (1997).
[74] Ishibe, S., Joly, D., Zhu, X. & Cantley, L. G. Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis. Mol Cell 12, 1275-85 (2003).
[75] Subauste, M. C., Pertz, O., Adamson, E. D., Turner, C. E., Junger, S. & Hahn, K. M. Vinculin modulation of paxillin-FAK interactions regulates ERK to control survival and motility. J Cell Biol 165, 371-81 (2004).
[76] Liu, Z. X., Yu, C. F., Nickel, C., Thomas, S. & Cantley, L. G. Hepatocyte growth factor induces ERK-dependent paxillin phosphorylation and regulates paxillin-focal adhesion kinase association. J Biol Chem 277, 10452-8 (2002).
[77] Chou, F. L., Hill, J. M., Hsieh, J. C., Pouyssegur, J., Brunet, A., Glading, A., Uberall, F., Ramos, J. W., Werner, M. H. & Ginsberg, M. H. PEA-15 binding to ERK1/2 MAPKs is required for its modulation of integrin activation. J Biol Chem 278, 52587-97 (2003).
[78] Hughes, P. E., Renshaw, M. W., Pfaff, M., Forsyth, J., Keivens, V. M., Schwartz, M. A. & Ginsberg, M. H. Suppression of integrin activation: a novel function of a Ras/Raf-initiated MAP kinase pathway. Cell 88,521-30 (1997).
[79] Klemke, R. L., Cai, S., Giannini, A. L., Gallagher, P. J., de Lanerolle, P. & Cheresh, D. A. Regulation of cell motility by mitogen-activated protein kinase. J Cell Biol 137,481-92(1997).
[80] Wu, W. S., Wu, J. R. & Hu, C. T. Signal cross talks for sustained MAPK activation and cell migration: the potential role of reactive oxygen species. Cancer Metastasis Rev 27, 303-14 (2008).
[81] Hunger-Glaser, I., Salazar, E. P., Sinnett-Smith, J. & Rozengurt, E. Bombesin, lysophosphatidic acid, and epidermal growth factor rapidly stimulate focal adhesion kinase phosphorylation at Ser-910: requirement for ERK activation. J Biol Chem 278, 22631-43 (2003).
[82] Frodin, M. & Gammeltoft, S. Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction. Mol Cell Endocrinol 151, 65-77 (1999).
[83] Deak, M., Clifton, A. D., Lucocq, L. M. & Alessi, D. R. Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. Embo J 17, 4426-41 (1998).
[84] Glading, A., Bodnar, R. J., Reynolds, I. J., Shiraha, H., Satish, L., Potter, D. A., Blair, H. C. & Wells, A. Epidermal growth factor activates m-calpain (calpain Ⅱ), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation. Mol Cell Biol 24,2499-512 (2004).
[85] Carragher, N. O., Westhoff, M. A., Fincham, V. J., Schaller, M. D. & Frame, M. C. A novel role for FAK as a protease-targeting adaptor protein: regulation by p42 ERK and Src. Curr Biol 13, 1442-50 (2003).
[86] Pullikuth, A., McKinnon, E., Schaeffer, H. J. & Catling, A. D. The MEK1 scaffolding protein MP1 regulates cell spreading by integrating PAK1 and Rho signals. Mol Cell Biol 25, 5119-33 (2005).
[87] Vial, E., Sahai, E. & Marshall, C. J. ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility. Cancer Cell 4, 67-79 (2003).
[88] Stahle, M., Veit, C, Bachfischer, U., Schierling, K., Skripczynski, B., Hall, A., Gierschik, P. & Giehl, K. Mechanisms in LPA-induced tumor cell migration: critical role of phosphorylated ERK. J Cell Sci 116, 3835-46 (2003).
[89] Sahai, E., Olson, M. F. & Marshall, C. J. Cross-talk between Ras and Rho signalling pathways in transformation favours proliferation and increased motility. Embo J 20, 755-66 (2001).
[1] Montell, D. J. Border-cell migration: the race is on. Nat Rev Mol Cell Biol 4, 13-24 (2003).
[2] Montell, D. J. The genetics of cell migration in Drosophila melanogaster and Caenorhabditis elegans development. Development 126,3035-46 (1999).
[3] Gilbert, S. F. The morphogenesis of evolutionary developmental biology. Int J Dev Biol 47,467-77 (2003).
[4] Keller, R. Cell migration during gastrulation. Curr Opin Cell Biol 17, 533-41 (2005).
[5] Lehmann, R. Cell migration in invertebrates: clues from border and distal tip cells. Curr Opin Genet Dev 11,457-63 (2001).
[6] Locascio, A. & Nieto, M. A. Cell movements during vertebrate development: integrated tissue behaviour versus individual cell migration. Curr Opin Genet Dev 11,464-9(2001).
[7] Marin, O. & Rubenstein, J. L. A long, remarkable journey: tangential migration in the telencephalon. Nat Rev Neurosci 2, 780-90 (2001).
[8] Brown, H. O., Levine, M. L. & Lipkin, M. Inhibition of intestinal epithelial cell renewal and migration induced by starvation. Am J Physiol 205, 868-72 (1963).
[9] Kunz, J. Proliferation, migration and cell renewal within the arterial wall. Acta Histochem Suppl 27,233-43 (1983).
[10] Decombas, M., Bonifay, P. & Kaqueler, J. C. [The role of hypocalcemia on cell renewal and migration in the oral epithelium of the rat]. J Biol Buccale 5, 245-59 (1977).
[11] Hattori, T. & Fujita, S. Tritiated thymidine autoradiographic study of cell migration and renewal in the pyloric mucosa of golden hamsters. Cell Tissue Res 175, 49-57 (1976).
[12] Stokowski, A., Shi, S., Sun, T., Bartold, P. M., Koblar, S. A. & Gronthos, S. EphB/ephrin-B interaction mediates adult stem cell attachment, spreading, and migration: implications for dental tissue repair. Stem Cells 25,156-64 (2007).
[13] Christensen, S. T., Pedersen, S. F., Satir, P., Veland, I. R. & Schneider, L. The primary cilium coordinates signaling pathways in cell cycle control and migration during development and tissue repair. Curr Top Dev Biol 85, 261-301 (2008).
[14] Pinco, K. A., He, W. & Yang, J. T. alpha4betal integrin regulates lamellipodia protrusion via a focal complex/focal adhesion-independent mechanism. Mol Biol Cell 13, 3203-17 (2002).
[15] Szekanecz, Z. & Koch, A. E. Cell-cell interactions in synovitis. Endothelial cells and immune cell migration. Arthritis Res 2, 368-73 (2000).
[16] Stachowiak, A. N. & Irvine, D. J. Inverse opal hydrogel-collagen composite scaffolds as a supportive microenvironment for immune cell migration. J Biomed Mater Res A 85, 815-28 (2008).
[17] Vicente-Manzanares, M., Sancho, D., Yanez-Mo, M. & Sanchez-Madrid, F. The leukocyte cytoskeleton in cell migration and immune interactions. Int Rev Cytol 216,233-89 (2002).
[18] Xiong, Y., Cao, C, Makarova, A., Hyman, B. & Zhang, L. Mac-1 promotes FcgammaRIIA-dependent cell spreading and migration on immune complexes. Biochemistry 45, 8721-31 (2006).
[19] Wang, H. W., Tedla, N., Lloyd, A. R., Wakefield, D. & McNeil, P. H. Mast cell activation and migration to lymph nodes during induction of an immune response in mice. J Clin Invest 102,1617-26 (1998).
[20] Westerberg, L., Larsson, M., Hardy, S. J., Fernandez, C, Thrasher, A. J. & Severinson, E. Wiskott-Aldrich syndrome protein deficiency leads to reduced B-cell adhesion, migration, and homing, and a delayed humoral immune response. Blood 105,1144-52 (2005).
[21] Luster, A. D., Alon, R. & von Andrian, U. H. Immune cell migration in inflammation: present and future therapeutic targets. Nat Immunol 6, 1182-90 (2005).
[22] Jones, G. E. Cellular signaling in macrophage migration and chemotaxis. J Leukoc Biol 68, 593-602 (2000).
[23] Kinashi, T. & Katagiri, K. Regulation of immune cell adhesion and migration by regulator of adhesion and cell polarization enriched in lymphoid tissues. Immunology 116, 164-71 (2005).
[24] Raines, E. W. The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease. Int J Exp Pathol 81, 173-82(2000).
[25] Cheong, A., Wood, I. C. & Beech, D. J. Less REST, more vascular disease? Regulation of cell cycle and migration of vascular smooth muscle cells. Cell Cycle 5,129-31(2006).
[26] Roque, M., Reis, E. D. & Roig, E. Role of smooth muscle cell migration and proliferation in allograft vascular disease. Transplant Proc 34, 333-4 (2002).
[27] McCarty, M. F. Thalidomide may impede cell migration in primates by down-regulating integrin beta-chains: potential therapeutic utility in solid malignancies, proliferative retinopathy, inflammatory disorders, neointimal hyperplasia, and osteoporosis. Med Hypotheses 49,123-31 (1997).
[28] Desmetz, C., Lin, Y. L., Mettling, C., Portales, P., Noel, D., Clot, J., Jorgensen, C. & Corbeau, P. Cell surface CCR5 density determines the intensity of T cell migration towards rheumatoid arthritis synoviocytes. Clin Immunol 123, 148-54 (2007).
[29] Woods, J. M., Klosowska, K., Spoden, D. J., Stumbo, N. G., Paige, D. J., Scatizzi, J. C., Volin, M. V., Rao, M. S. & Perlman, H. A cell-cycle independent role for p21 in regulating synovial fibroblast migration in rheumatoid arthritis. Arthritis Res Ther 8, R113 (2006).
[30] Ingegnoli, F., Blades, M., Manzo, A., Wahid, S., Perretti, M., Panayi, G. & Pitzalis, C. [Role of cell migration in the pathogenesis of rheumatoid arthritis: in vivo studies in SCID mice transplanted with human synovial membrane]. Reumatismo 54, 128-32 (2002).
[31] Mclnnes, I. B., al-Mughales, J., Field, M., Leung, B. P., Huang, F. P., Dixon, R., Sturrock, R. D., Wilkinson, P. C. & Liew, F. Y. The role of interleukin-15 in T-cell migration and activation in rheumatoid arthritis. Nat Med 2, 175-82 (1996).
[32] Zang, Y. C., Samanta, A. K., Haider, J. B., Hong, J., Tejada-Simon, M. V., Rivera, V. M. & Zhang, J. Z. Aberrant T cell migration toward RANTES and MIP-1 alpha in patients with multiple sclerosis. Overexpression of chemokine receptor CCR5. Brain 123 (Pt 9), 1874-82 (2000).
[33] Marracci, G. H., McKeon, G. P., Marquardt, W. E., Winter, R. W., Riscoe, M. K. & Bourdette, D. N. Alpha lipoic acid inhibits human T-cell migration: implications for multiple sclerosis. J Neurosci Res 78, 362-70 (2004).
[34] Dressel, A., Mirowska-Guzel, D., Gerlach, C. & Weber, F. Migration of T-cell subsets in multiple sclerosis and the effect of interferon-betala. Acta Neurol Scand 116, 164-8(2007).
[35] Tischner, D., Weishaupt, A., van den Brandt, J., Muller, N., Beyersdorf, N., Ip, C. W., Toyka, K. V., Hunig, T., Gold, R., Kerkau, T. & Reichardt, H. M. Polyclonal expansion of regulatory T cells interferes with effector cell migration in a model of multiple sclerosis. Brain 129,2635-47 (2006).
[36] Sinha, S., Subramanian, S., Proctor, T. M., Kaler, L. J., Grafe, M., Dahan, R., Huan, J., Vandenbark, A. A., Burrows, G. G. & Offher, H. A promising therapeutic approach for multiple sclerosis: recombinant T-cell receptor ligands modulate experimental autoimmune encephalomyelitis by reducing interleukin-17 production and inhibiting migration of encephalitogenic cells into the CNS. J Neurosci 27, 12531-9 (2007).
[37] Milner, R. Understanding the molecular basis of cell migration; implications for clinical therapy in multiple sclerosis. Clin Sci (Lond) 92, 113-22 (1997).
[38] Yamaguchi, H., Wyckoff, J. & Condeelis, J. Cell migration in tumors. Curr Opin Cell Biol 17, 559-64 (2005).
[39] Wang, W., Goswami, S., Sahai, E., Wyckoff, J. B., Segall, J. E. & Condeelis, J. S. Tumor cells caught in the act of invading: their strategy for enhanced cell motility. Trends Cell Biol 15, 138-45 (2005).
[40] Kerjan, G. & Gleeson, J. G. Moving neurons back into place. Nat Med 15, 17-8(2009).
[41] Kreis, P. & Barnier, J. V. PAK signalling in neuronal physiology. Cell Signal 21, 384-93 (2009).
[42] Lauffenburger, D. A. & Horwitz, A. F. Cell migration: a physically integrated molecular process. Cell 84, 359-69 (1996).
[43] Sheetz, M. P., Felsenfeld, D., Galbraith, C. G. & Choquet, D. Cell migration as a five-step cycle. Biochem Soc Symp 65, 233-43 (1999).
[44] Ridley, A. J., Schwartz, M. A., Burridge, K., Firtel, R. A., Ginsberg, M. H., Borisy, G., Parsons, J. T. & Horwitz, A. R. Cell migration: integrating signals from front to back. Science 302, 1704-9 (2003).
[45] Huang, C., Jacobson, K. & Schaller, M. D. MAP kinases and cell migration. J Cell Sci 117,4619-28(2004).
[46] Knight, B., Laukaitis, C, Akhtar, N., Hotchin, N. A., Edlund, M. & Horwitz, A. R. Visualizing muscle cell migration in situ. Curr Biol 10, 576-85 (2000).
[47] Friedl, P. & Wolf, K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3, 362-74 (2003).
[48] Pollard, T. D. & Borisy, G. G. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112,453-65 (2003).
[49] Koestler, S. A., Auinger, S., Vinzenz, M., Rottner, K. & Small, J. V. Differentially oriented populations of actin filaments generated in lamellipodia collaborate in pushing and pausing at the cell front. Nat Cell Biol 10, 306-13 (2008).
[50] Nemethova, M., Auinger, S. & Small, J. V. Building the actin cytoskeleton: filopodia contribute to the construction of contractile bundles in the lamella. J Cell Biol 180, 1233-44(2008).
[51] dos Remedios, C. G., Chhabra, D., Kekic, M., Dedova, I. V., Tsubakihara, M., Berry, D. A. & Nosworthy, N. J. Actin binding proteins: regulation of cytoskeletal microfilaments. Physiol Rev 83, 433-73 (2003).
[52] Akin, O. & Mullins, R. D. Capping protein increases the rate of actin-based motility by promoting filament nucleation by the Arp2/3 complex. Cell 133, 841-51 (2008).
[53] Etienne-Manneville, S. & Hall, A. Rho GTPases in cell biology. Nature 420, 629-35 (2002).
[54] Cory, G. O. & Ridley, A. J. Cell motility: braking WAVEs. Nature 418, 732-3 (2002).
[55] Snapper, S. B., Takeshima, F., Anton, I., Liu, C. H., Thomas, S. M., Nguyen, D., Dudley, D., Fraser, H., Purich, D., Lopez-Ilasaca, M., Klein, C, Davidson, L., Bronson, R., Mulligan, R. C., Southwick, F., Geha, R., Goldberg, M. B., Rosen, F. S., Hartwig, J. H. & Alt, F. W. N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility. Nat Cell Biol 3, 897-904 (2001).
[56] Katoh, H. & Negishi, M. RhoG activates Racl by direct interaction with the Dock180-binding protein Elmo. Nature 424, 461-4 (2003).
[57] Soderling, S. H., Binns, K. L., Wayman, G. A., Davee, S. M., Ong, S. H., Pawson, T. & Scott, J. D. The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling. Nat Cell Biol 4, 970-5 (2002).
[58] Cory, G. O., Garg, R., Cramer, R. & Ridley, A. J. Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome protein. J Biol Chem 277, 45115-21(2002).
[59] Hussain, N. K., Jenna, S., Glogauer, M., Quinn, C. C., Wasiak, S., Guipponi, M., Antonarakis, S. E., Kay, B. K., Stossel, T. P., Lamarche-Vane, N. & McPherson, P. S. Endocytic protein intersectin-1 regulates actin assembly via Cdc42 and N-WASP. Nat Cell Biol 3, 927-32 (2001).
[60] Suetsugu, S., Hattori, M., Miki, H., Tezuka, T., Yamamoto, T., Mikoshiba, K. & Takenawa, T. Sustained activation of N-WASP through phosphorylation is essential for neurite extension. Dev Cell 3, 645-58 (2002).
[61] Moreau, V., Frischknecht, F., Reckmann, I., Vincentelli, R., Rabut, G., Stewart, D. & Way, M. A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization. Nat Cell Biol 2, 441-8 (2000).
[62] Sasahara, Y., Rachid, R., Byrne, M. J., de la Fuente, M. A., Abraham, R. T., Ramesh, N. & Geha, R. S. Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation. Mol Cell 10, 1269-81 (2002).
[63] Itoh, R. E., Kurokawa, K., Ohba, Y., Yoshizaki, H., Mochizuki, N. & Matsuda, M. Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells. Mol Cell Biol 22, 6582-91 (2002).
[64] Srinivasan, S., Wang, F., Glavas, S., Ott, A., Hofmann, F., Aktories, K., Kalman, D. & Bourne, H. R. Rac and Cdc42 play distinct roles in regulating PI(3,4,5)P3 and polarity during neutrophil chemotaxis. J Cell Biol 160, 375-85 (2003).
[65] Rodriguez, O. C., Schaefer, A. W., Mandato, C. A., Forscher, P., Bement, W. M. & Waterman-Storer, C. M. Conserved microtubule-actin interactions in cell movement and morphogenesis. Nat Cell Biol 5, 599-609 (2003).
[66] Serrador, J. M., Nieto, M. & Sanchez-Madrid, F. Cytoskeletal rearrangement during migration and activation of T lymphocytes. Trends Cell Biol 9, 228-33 (1999).
[67] Etienne-Manneville, S. & Hall, A. Cell polarity: Par6, aPKC and cytoskeletal crosstalk. Curr Opin Cell Biol 15, 67-72 (2003).
[68] Li, Z., Hannigan, M., Mo, Z., Liu, B., Lu, W., Wu, Y., Smrcka, A. V., Wu, G., Li, L., Liu, M., Huang, C. K. & Wu, D. Directional sensing requires G beta gamma-mediated PAK1 and PIX alpha-dependent activation of Cdc42. Cell 114,215-27(2003).
[69] Etienne-Manneville, S. & Hall, A. Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. Cell 106, 489-98 (2001).
[70] Devreotes, P. & Janetopoulos, C. Eukaryotic chemotaxis: distinctions between directional sensing and polarization. J Biol Chem 278, 20445-8 (2003).
[71] Merlot, S. & Firtel, R. A. Leading the way: Directional sensing through phosphatidylinositol 3-kinase and other signaling pathways. J Cell Sci 116, 3471-8(2003).
[72] Welch, H. C., Coadwell, W. J., Stephens, L. R. & Hawkins, P. T. Phosphoinositide 3-kinase-dependent activation of Rac. FEBS Lett 546, 93-7 (2003).
[73] del Pozo, M. A., Price, L. S., Alderson, N. B., Ren, X. D. & Schwartz, M. A. Adhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK. Embo J 19, 2008-14 (2000).
[74] Kiosses, W. B., Shattil, S. J., Pampori, N. & Schwartz, M. A. Rac recruits high-affinity integrin alphavbeta3 to lamellipodia in endothelial cell migration. Nat Cell Biol 3, 316-20 (2001).
[75] Schwartz, M. A. & Shattil, S. J. Signaling networks linking integrins and rho family GTPases. Trends Biochem Sci 25, 388-91 (2000).
[76] Shattil, S. J. Function and regulation of the beta 3 integrins in hemostasis and vascular biology. Thromb Haemost 74, 149-55 (1995).
[77] Small, J. V. & Kaverina, I. Microtubules meet substrate adhesions to arrange cell polarity. Curr Opin Cell Biol 15,40-7 (2003).
[78] Evers, E. E., Zondag, G. C., Malliri, A., Price, L. S., ten Klooster, J. P., van der Kammen, R. A. & Collard, J. G. Rho family proteins in cell adhesion and cell migration. Eur J Cancer 36,1269-74 (2000).
[79] Worthylake, R. A. & Burridge, K. RhoA and ROCK promote migration by limiting membrane protrusions. J Biol Chem 278, 13578-84 (2003).
[80] Xu, J., Wang, F., Van Keymeulen, A., Herzmark, P., Straight, A., Kelly, K. Takuwa, Y., Sugimoto, N., Mitchison, T. & Bourne, H. R. Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell 114,201-14(2003).
[81] Gardiner, E. M., Pestonjamasp, K. N., Bohl, B. P., Chamberlain, C., Hahn, K. M. & Bokoch, G. M. Spatial and temporal analysis of Rac activation during live neutrophil chemotaxis. Curr Biol 12,2029-34 (2002).
[82] Tsuji, T., Ishizaki, T., Okamoto, M., Higashida, C., Kimura, K., Furuyashiki, T., Arakawa, Y., Birge, R. B., Nakamoto, T., Hirai, H. & Narumiya, S. ROCK and mDial antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts. J Cell Biol 157, 819-30 (2002).
[83] Geiger, B., Bershadsky, A., Pankov, R. & Yamada, K. M. Transmembrane crosstalk between the extracellular matrix-cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2, 793-805 (2001).
[84] Emsley, J., Knight, C. G., Farndale, R. W., Barnes, M. J. & Liddington, R. C. Structural basis of collagen recognition by integrin alpha2betal. Cell 101, 47-56 (2000).
[85] Kim, M., Carman, C. V. & Springer, T. A. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 301, 1720-5 (2003).
[86] Kinbara, K., Goldfinger, L. E., Hansen, M., Chou, F. L. & Ginsberg, M. H. Ras GTPases: integrins' friends or foes? Nat Rev Mol Cell Biol 4, 767-76 (2003).
[87] Tadokoro, S., Shattil, S. J., Eto, K., Tai, V., Liddington, R. C, de Pereda, J. M., Ginsberg, M. H. & Calderwood, D. A. Talin binding to integrin beta tails: a final common step in integrin activation. Science 302, 103-6 (2003).
[88] Goldfinger, L. E., Han, J., Kiosses, W. B., Howe, A. K. & Ginsberg, M. H. Spatial restriction of alpha4 integrin phosphorylation regulates lamellipodial stability and alpha4betal-dependent cell migration. J Cell Biol 162, 731-41 (2003).
[89] Webb, D. J., Parsons, J. T. & Horwitz, A. F. Adhesion assembly, disassembly and turnover in migrating cells - over and over and over again. Nat Cell Biol 4,E97-100(2002).
[90] Beningo, K. A., Dembo, M, Kaverina, I., Small, J. V. & Wang, Y. L. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J Cell Biol 153, 881-8 (2001).
[91] Galbraith, C. G., Yamada, K. M. & Sheetz, M. P. The relationship between force and focal complex development. J Cell Biol 159, 695-705 (2002).
[92] Riento, K. & Ridley, A. J. Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 4,446-56 (2003).
[93] Balaban, N. Q., Schwarz, U. S., Riveline, D., Goichberg, P., Tzur, G., Sabanay, I., Mahalu, D., Safran, S., Bershadsky, A., Addadi, L. & Geiger, B. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat Cell Biol 3,466-72 (2001).
[94] Larsen, M., Tremblay, M. L. & Yamada, K. M. Phosphatases in cell-matrix adhesion and migration. Nat Rev Mol Cell Biol 4, 700-11 (2003).
[95] Alahari, S. K., Reddig, P. J. & Juliano, R. L. Biological aspects of signal transduction by cell adhesion receptors. Int Rev Cytol 220, 145-84 (2002).
[96] Turner, C. E., West, K. A. & Brown, M. C. Paxillin-ARF GAP signaling and the cytoskeleton. Curr Opin Cell Biol 13, 593-9 (2001).
[97] Brahmbhatt, A. A. & Klemke, R. L. ERK and RhoA differentially regulate pseudopodia growth and retraction during chemotaxis. J Biol Chem 278, 13016-25 (2003).
[98] Chung, C. Y., Potikyan, G. & Firtel, R. A. Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa. Mol Cell 7, 937-47 (2001).
[99] Lee, J., Ishihara, A., Oxford, G., Johnson, B. & Jacobson, K. Regulation of cell movement is mediated by stretch-activated calcium channels. Nature 400, 382-6 (1999).
[100] Glading, A., Lauffenburger, D. A. & Wells, A. Cutting to the chase: calpain proteases in cell motility. Trends Cell Biol 12,46-54 (2002).
[101] Ridley, A. J. Rho GTPases and cell migration. J Cell Sci 114, 2713-22 (2001).
[102] Webb, D. J., Donais, K., Whitmore, L. A., Thomas, S. M., Turner, C. E., Parsons, J. T. & Horwitz, A. F. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol 6, 154-61 (2004).
[103] Hood, J. D. & Cheresh, D. A. Role of integrins in cell invasion and migration. Nat Rev Cancer 2, 91-100 (2002).
[104] Howe, A. K. & Juliano, R. L. Regulation of anchorage-dependent signal transduction by protein kinase A and p21-activated kinase. Nat Cell Biol 2, 593-600 (2000).
[105] Weaver, A. M., Young, M. E., Lee, W. L. & Cooper, J. A. Integration of signals to the Arp2/3 complex. Curr Opin Cell Biol 15,23-30 (2003).
[106] Vartiainen, M. K. & Machesky, L. M. The WASP-Arp2/3 pathway: genetic insights. Curr Opin Cell Biol 16, 174-81 (2004).
[107] Watanabe, N. & Higashida, C. Formins: processive cappers of growing actin filaments. Exp Cell Res 301, 16-22 (2004).
[108] Krause, M., Dent, E. W., Bear, J. E., Loureiro, J. J. & Gertler, F. B. Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration. Annu Rev Cell Dev Biol 19, 541-64 (2003).
[109] Jaffe, A. B. & Hall, A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21,247-69 (2005).
[110] Wittmann, T., Bokoch, G. M. & Waterman-Storer, C. M. Regulation of microtubule destabilizing activity of Op18/stathmin downstream of Racl. J Biol Chem 279, 6196-203 (2004).
[111] Gomes, E. R., Jani, S. & Gundersen, G. G. Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Cell 121, 451-63 (2005).
[112] Ezratty, E. J., Partridge, M. A. & Gundersen, G. G. Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol 7, 581-90 (2005).
[113] Franco, S. J., Rodgers, M. A., Perrin, B. J., Han, J., Bennin, D. A., Critchley, D. R. & Huttenlocher, A. Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nat Cell Biol 6, 977-83 (2004).
[114] Olson, M. F. & Sahai, E. The actin cytoskeleton in cancer cell motility. Clin Exp Metastasis 26, 273-87 (2009).
[115] Brooks, S. A., Lomax-Browne, H. J., Carter, T. M., Kinch, C. E. & Hall, D. M. Molecular interactions in cancer cell metastasis. Acta Histochem (2009).
[116] Chiang, A. C. & Massague, J. Molecular basis of metastasis. N Engl J Med 359,2814-23(2008).
[2] Knaus, U. G & Bokoch, G M. The p21Rac/Cdc42-activated kinases (PAKs). Int J Biochem Cell Biol 30, 857-62 (1998).
[3] Bokoch, G. M. Biology of the p21-activated kinases. Annu Rev Biochem 72, 743-81 (2003).
[4] Kumar, R. & Vadlamudi, R. K. Emerging functions of p21-activated kinases in human cancer cells. J Cell Physiol 193,133-44 (2002).
[5] Leberer, E., Thomas, D. Y. & Whiteway, M. Pheromone signalling and polarized morphogenesis in yeast. Curr Opin Genet Dev 7, 59-66 (1997).
[6] Jaffer, Z. M. & Chernoff, J. p21-activated kinases: three more join the Pak. Int J Biochem Cell Biol 34, 713-7 (2002).
[7] Dan, C, Nath, N., Liberto, M. & Minden, A. PAK5, a new brain-specific kinase, promotes neurite outgrowth in N1E-115 cells. Mol Cell Biol 22, 567-77 (2002).
[8] Parrini, M. C, Lei, M., Harrison, S. C. & Mayer, B. J. Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Racl. Mol Cell 9, 73-83 (2002).
[9] Chong, C., Tan, L., Lim, L. & Manser, E. The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity. J Biol Chem 276, 17347-53 (2001).
[10] Buchwald, G., Hostinova, E., Rudolph, M. G., Kraemer, A., Sickmann, A., Meyer, H. E., Scheffzek, K. & Wittinghofer, A. Conformational switch and role of phosphorylation in PAK activation. Mol Cell Biol 21, 5179-89 (2001).
[11] Dharmawardhane, S., Sanders, L. C., Martin, S. S., Daniels, R. H. & Bokoch, G. M. Localization of p21-activated kinase 1 (PAK1) to pinocytic vesicles and cortical actin structures in stimulated cells. J Cell Biol 138, 1265-78 (1997).
[12] Sells, M. A., Pfaff, A. & Chernoff, J. Temporal and spatial distribution of activated Pak1 in fibroblasts. J Cell Biol 151, 1449-58 (2000).
[13] Sells, M. A., Knaus, U. G., Bagrodia, S., Ambrose, D. M., Bokoch, G. M. & Chernoff, J. Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells. Curr Biol 7,202-10 (1997).
[14] Sells, M. A., Boyd, J. T. & Chernoff, J. p21 -activated kinase 1 (Pak1) regulates cell motility in mammalian fibroblasts. J Cell Biol 145, 837-49 (1999).
[15] Manser, E., Huang, H. Y., Loo, T. H., Chen, X. Q., Dong, J. M., Leung, T. & Lim, L. Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes. Mol Cell Biol 17, 1129-43 (1997).
[16] Frost, J. A., Khokhlatchev, A., Stippec, S., White, M. A. & Cobb, M. H. Differential effects of PAK1-activating mutations reveal activity-dependent and -independent effects on cytoskeletal regulation. J Biol Chem 273, 28191-8 (1998).
[17] Kiosses, W. B., Daniels, R. H., Otey, C, Bokoch, G M. & Schwartz, M. A. A role for p21-activated kinase in endothelial cell migration. J Cell Biol 147, 831-44(1999).
[18] Edwards, D. C., Sanders, L. C., Bokoch, G. M. & Gill, G. N. Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nat Cell Biol 1,253-9 (1999).
[19] Sanders, L. C., Matsumura, F., Bokoch, G. M. & de Lanerolle, P. Inhibition of myosin light chain kinase by p21-activated kinase. Science 283, 2083-5 (1999).
[20] Vadlamudi, R. K., Li, F., Adam, L., Nguyen, D., Ohta, Y., Stossel, T. P. & Kumar, R. Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1. Nat Cell Biol 4, 681-90 (2002).
[21] Wittmann, T., Bokoch, G. M. & Waterman-Storer, C. M. Regulation of leading edge microtubule and actin dynamics downstream of Racl. J Cell Biol 161, 845-51 (2003).
[22] Krueger, J. S., Keshamouni, V. G, Atanaskova, N. & Reddy, K. B. Temporal and quantitative regulation of mitogen-activated protein kinase (MAPK) modulates cell motility and invasion. Oncogene 20, 4209-18 (2001).
[23] Jo, M., Thomas, K. S., Somlyo, A. V., Somlyo, A. P. & Gonias, S. L. Cooperativity between the Ras-ERK and Rho-Rho kinase pathways in urokinase-type plasminogen activator-stimulated cell migration. J Biol Chem 277, 12479-85 (2002).
[24] Huang, C., Jacobson, K. & Schaller, M. D. MAP kinases and cell migration. J Cell Sci 117, 4619-28 (2004).
[25] Webb, D. J., Donais, K., Whitmore, L. A., Thomas, S. M., Turner, C. E., Parsons, J. T. & Horwitz, A. F. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol 6,154-61 (2004).
[26] Slack-Davis, J. K., Eblen, S. T., Zecevic, M., Boerner, S. A., Tarcsafalvi, A., Diaz, H. B., Marshall, M. S., Weber, M. J., Parsons, J. T. & Catling, A. D. PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation. J Cell Biol 162, 281-91 (2003).
[27] Jin, S., Zhuo, Y., Guo, W. & Field, J. p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association. J Biol Chem 280, 24698-705 (2005).
[28] Sundberg-Smith, L. J., Doherty, J. T., Mack, C. P. & Taylor, J. M. Adhesion stimulates direct PAK1/ERK2 association and leads to ERK-dependent PAK1 Thr212 phosphorylation. J Biol Chem 280, 2055-64 (2005).
[29] Chen, W, Chen, S., Yap, S. F. & Lim, L. The Caenorhabditis elegans p21-activated kinase (CePAK) colocalizes with CeRac1 and CDC42Ce at hypodermal cell boundaries during embryo elongation. J Biol Chem 271, 26362-8 (1996).
[30] Melzig, J., Rein, K. H., Schafer, U., Pfister, H., Jackie, H., Heisenberg, M. & Raabe, T. A protein related to p21-activated kinase (PAK) that is involved in neurogenesis in the Drosophila adult central nervous system. Curr Biol 8, 1223-6 (1998).
[31] Hing, H., Xiao, J., Harden, N., Lim, L. & Zipursky, S. L. Pak functions downstream of Dock to regulate photoreceptor axon guidance in Drosophila. Cell 97, 853-63 (1999).
[32] Chung, C. Y. & Firtel, R. A. PAKa, a putative PAK family member, is required for cytokinesis and the regulation of the cytoskeleton in Dictyostelium discoideum cells during chemotaxis. J Cell Biol 147, 559-76 (1999).
[33] Leberer, E., Ziegelbauer, K., Schmidt, A., Harcus, D., Dignard, D., Ash, J., Johnson, L. & Thomas, D. Y. Virulence and hyphal formation of Candida albicans require the Ste20p-like protein kinase CaCla4p. Curr Biol 7, 539-46 (1997).
[34] Burridge, K. Crosstalk between Rac and Rho. Science 283, 2028-9 (1999).
[35] Chrzanowska-Wodnicka, M. & Burridge, K. Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J Cell Biol 133, 1403-15 (1996).
[36] Waterman-Storer, C. M., Worthylake, R. A., Liu, B. P., Burridge, K. & Salmon, E. D. Microtubule growth activates Racl to promote lamellipodial protrusion in fibroblasts. Nat Cell Biol 1,45-50 (1999).
[37] Krendel, M., Zenke, F. T. & Bokoch, G M. Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton. Nat Cell Biol 4, 294-301 (2002).
[38] Banga, S. S., Yamamoto, A. H., Mason, J. M. & Boyd, J. B. Molecular cloning of mei-41, a gene that influences both somatic and germline chromosome metabolism of Drosophila melanogaster. Mol Gen Genet 246, 148-55 (1995).
[39] Haring, H. [Pathophysiology of insulin resistance]. Herz 20, 5-15 (1995).
[40] Bonthron, D. T., Hayward, B. E., Moran, V. & Strain, L. Characterization of TH1 and CTSZ, two non-imprinted genes downstream of GNAS1 in chromosome 20q13. Hum Genet 107, 165-75 (2000).
[41] Liu, W., Shen, X., Yang, Y, Yin, X., Xie, J., Yan, J., Jiang, J., Liu, W., Wang, H., Sun, M., Zheng, Y. & Gu, J. Trihydrophobin 1 is a new negative regulator of A-Raf kinase. J Biol Chem 279, 10167-75 (2004).
[42] Yang, Y, Liu, W., Zou, W., Wang, H., Zong, H., Jiang, J., Wang, Y. & Gu, J. Ubiquitin-dependent proteolysis of trihydrophobin 1 (TH1) by the human papilloma virus E6-associated protein (E6-AP). J Cell Biochem 101, 167-80 (2007).
[43] Yamaguchi, Y, Takagi, T., Wada, T., Yano, K., Furuya, A., Sugimoto, S., Hasegawa, J. & Handa, H. NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase Ⅱ elongation. Cell 97, 41-51 (1999).
[44] Narita, T., Yamaguchi, Y, Yano, K., Sugimoto, S., Chanarat, S., Wada, T., Kim, D. K., Hasegawa, J., Omori, M., Inukai, N., Endoh, M., Yamada, T. & Handa, H. Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex. Mol Cell Biol 23, 1863-73(2003).
[45] Wu, C. H., Yamaguchi, Y, Benjamin, L. R., Horvat-Gordon, M., Washinsky, J., Enerly, E., Larsson, J., Lambertsson, A., Handa, H. & Gilmour, D. NELF and DSIF cause promoter proximal pausing on the hsp70 promoter in Drosophila. Genes Dev 17, 1402-14(2003).
[46] Aiyar, S. E., Sun, J. L., Blair, A. L., Moskaluk, C. A., Lu, Y. Z., Ye, Q. N., Yamaguchi, Y, Mukherjee, A., Ren, D. M., Handa, H. & Li, R. Attenuation of estrogen receptor alpha-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor. Genes Dev 18, 2134-46 (2004).
[47] Alahari, S. K., Reddig, P. J. & Juliano, R. L. The integrin-binding protein Nischarin regulates cell migration by inhibiting PAK. Embo J 23, 2777-88 (2004).
[48] Lei, M., Robinson, M. A. & Harrison, S. C. The active conformation of the PAK1 kinase domain. Structure 13, 769-78 (2005).
[49] Lei, M., Lu, W., Meng, W., Parrini, M. C., Eck, M. J., Mayer, B. J. & Harrison, S. C. Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell 102, 387-97 (2000).
[50] Guo, D., Tan, Y. C., Wang, D., Madhusoodanan, K. S., Zheng, Y., Maack, T., Zhang, J. J. & Huang, X. Y. A Rac-cGMP signaling pathway. Cell 128, 341-55 (2007).
[51] Fincham, V. J., James, M., Frame, M. C. & Winder, S. J. Active ERK/MAP kinase is targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src. Embo J 19, 2911-23 (2000).
[52] Dharmawardhane, S., Brownson, D., Lennartz, M. & Bokoch, G. M. Localization of p21-activated kinase 1 (PAK1) to pseudopodia, membrane ruffles, and phagocytic cups in activated human neutrophils. J Leukoc Biol 66, 521-7(1999).
[53] Koestler, S. A., Auinger, S., Vinzenz, M, Rottner, K. & Small, J. V. Differentially oriented populations of actin filaments generated in lamellipodia collaborate in pushing and pausing at the cell front. Nat Cell Biol 10, 306-13 (2008).
[54] Nemethova, M., Auinger, S. & Small, J. V. Building the actin cytoskeleton: filopodia contribute to the construction of contractile bundles in the lamella. J Cell Biol 180, 1233-44 (2008).
[55] Serrels, B., Serrels, A., Brunton, V. G., Holt, M., McLean, G. W., Gray, C. H., Jones, G.E.& Frame, M. C. Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex. Nat Cell Biol 9, 1046-56 (2007).
[56] Ridley, A. J., Schwartz, M. A., Burridge, K., Firtel, R. A., Ginsberg, M. H., Borisy, G., Parsons, J. T. & Horwitz, A. R. Cell migration: integrating signals from front to back. Science 302,1704-9 (2003).
[57] Rayala, S. K., Talukder, A. H., Balasenthil, S., Tharakan, R., Barnes, C. J., Wang, R. A., Aldaz, M., Khan, S. & Kumar, R. P21-activated kinase 1 regulation of estrogen receptor-alpha activation involves serine 305 activation linked with serine 118 phosphorylation. Cancer Res 66,1694-701 (2006).
[58] Schrantz, N., da Silva Correia, J., Fowler, B., Ge, Q., Sun, Z. & Bokoch, G M. Mechanism of p21-activated kinase 6-mediated inhibition of androgen receptor signaling. J Biol Chem 279,1922-31 (2004).
[59] Lee, S. R., Ramos, S. M., Ko, A., Masiello, D., Swanson, K. D., Lu, M. L. & Balk, S. P. AR and ER interaction with a p21-activated kinase (PAK6). Mol Endocrinol 16, 85-99 (2002).
[60] Howe, A. K. & Juliano, R. L. Regulation of anchorage-dependent signal transduction by protein kinase A and p21-activated kinase. Nat Cell Biol 2, 593-600 (2000).
[61] Koh, C. G., Tan, E. J., Manser, E. & Lim, L. The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family. Curr Biol 12, 317-21 (2002).
[62] Zang, M., Hayne, C. & Luo, Z. Interaction between active Pakl and Raf-1 is necessary for phosphorylation and activation of Raf-1. J Biol Chem 277, 4395-405 (2002).
[63] King, B. H., Cromwell, H. C., Lee, H. T., Behrstock, S. P., Schmanke, T. & Maidment, N. T. Dopaminergic and glutamatergic interactions in the expression of self-injurious behavior. Dev Neurosci 20,180-7 (1998).
[64] Frost, J. A., Steen, H., Shapiro, P., Lewis, T., Ahn, N., Shaw, P. E. & Cobb, M. H. Cross-cascade activation of ERKs and ternary complex factors by Rho family proteins. Embo J 16, 6426-38 (1997).
[65] Kiosses, W. B., Shattil, S. J., Pampori, N. & Schwartz, M. A. Rac recruits high-affinity integrin alphavbeta3 to lamellipodia in endothelial cell migration. Nat Cell Biol 3, 316-20 (2001).
[66] Gabarra-Niecko, V., Schaller, M. D. & Dunty, J. M. FAK regulates biological processes important for the pathogenesis of cancer. Cancer Metastasis Rev 22, 359-74 (2003).
[67] Katz, M., Amit, I., Cirri, A., Shay, T., Carvalho, S., Lavi, S., Milanezi, F., Lyass, L., Amariglio, N., Jacob-Hirsch, J., Ben-Chetrit, N., Tarcic, G., Lindzen, M., Avraham, R., Liao, Y. C., Trusk, P., Lyass, A., Rechavi, G., Spector, N. L., Lo, S. H., Schmitt, F., Bacus, S. S. & Yarden, Y. A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration. Nat Cell Biol 9, 961-9 (2007).
[68] Geiger, B., Spatz, J. P. & Bershadsky, A. D. Environmental sensing through focal adhesions. Nat Rev Mol Cell Biol 10,21-33 (2009).
[69] Geiger, B., Bershadsky, A., Pankov, R. & Yamada, K. M. Transmembrane crosstalk between the extracellular matrix-cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2, 793-805 (2001).
[70] Emsley, J., Knight, C. G., Farndale, R. W., Barnes, M. J. & Liddington, R. C. Structural basis of collagen recognition by integrin alpha2betal. Cell 101, 47-56 (2000).
[71] Kim, M., Carman, C. V. & Springer, T. A. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 301, 1720-5 (2003).
[72] Huttenlocher, A., Ginsberg, M. H. & Horwitz, A. F. Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity. J Cell Biol 134,1551-62 (1996).
[73] Palecek, S. P., Loftus, J. C., Ginsberg, M. H., Lauffenburger, D. A. & Horwitz, A. F. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature 385, 537-40 (1997).
[74] Ishibe, S., Joly, D., Zhu, X. & Cantley, L. G. Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis. Mol Cell 12, 1275-85 (2003).
[75] Subauste, M. C., Pertz, O., Adamson, E. D., Turner, C. E., Junger, S. & Hahn, K. M. Vinculin modulation of paxillin-FAK interactions regulates ERK to control survival and motility. J Cell Biol 165, 371-81 (2004).
[76] Liu, Z. X., Yu, C. F., Nickel, C., Thomas, S. & Cantley, L. G. Hepatocyte growth factor induces ERK-dependent paxillin phosphorylation and regulates paxillin-focal adhesion kinase association. J Biol Chem 277, 10452-8 (2002).
[77] Chou, F. L., Hill, J. M., Hsieh, J. C., Pouyssegur, J., Brunet, A., Glading, A., Uberall, F., Ramos, J. W., Werner, M. H. & Ginsberg, M. H. PEA-15 binding to ERK1/2 MAPKs is required for its modulation of integrin activation. J Biol Chem 278, 52587-97 (2003).
[78] Hughes, P. E., Renshaw, M. W., Pfaff, M., Forsyth, J., Keivens, V. M., Schwartz, M. A. & Ginsberg, M. H. Suppression of integrin activation: a novel function of a Ras/Raf-initiated MAP kinase pathway. Cell 88,521-30 (1997).
[79] Klemke, R. L., Cai, S., Giannini, A. L., Gallagher, P. J., de Lanerolle, P. & Cheresh, D. A. Regulation of cell motility by mitogen-activated protein kinase. J Cell Biol 137,481-92(1997).
[80] Wu, W. S., Wu, J. R. & Hu, C. T. Signal cross talks for sustained MAPK activation and cell migration: the potential role of reactive oxygen species. Cancer Metastasis Rev 27, 303-14 (2008).
[81] Hunger-Glaser, I., Salazar, E. P., Sinnett-Smith, J. & Rozengurt, E. Bombesin, lysophosphatidic acid, and epidermal growth factor rapidly stimulate focal adhesion kinase phosphorylation at Ser-910: requirement for ERK activation. J Biol Chem 278, 22631-43 (2003).
[82] Frodin, M. & Gammeltoft, S. Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction. Mol Cell Endocrinol 151, 65-77 (1999).
[83] Deak, M., Clifton, A. D., Lucocq, L. M. & Alessi, D. R. Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. Embo J 17, 4426-41 (1998).
[84] Glading, A., Bodnar, R. J., Reynolds, I. J., Shiraha, H., Satish, L., Potter, D. A., Blair, H. C. & Wells, A. Epidermal growth factor activates m-calpain (calpain Ⅱ), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation. Mol Cell Biol 24,2499-512 (2004).
[85] Carragher, N. O., Westhoff, M. A., Fincham, V. J., Schaller, M. D. & Frame, M. C. A novel role for FAK as a protease-targeting adaptor protein: regulation by p42 ERK and Src. Curr Biol 13, 1442-50 (2003).
[86] Pullikuth, A., McKinnon, E., Schaeffer, H. J. & Catling, A. D. The MEK1 scaffolding protein MP1 regulates cell spreading by integrating PAK1 and Rho signals. Mol Cell Biol 25, 5119-33 (2005).
[87] Vial, E., Sahai, E. & Marshall, C. J. ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility. Cancer Cell 4, 67-79 (2003).
[88] Stahle, M., Veit, C, Bachfischer, U., Schierling, K., Skripczynski, B., Hall, A., Gierschik, P. & Giehl, K. Mechanisms in LPA-induced tumor cell migration: critical role of phosphorylated ERK. J Cell Sci 116, 3835-46 (2003).
[89] Sahai, E., Olson, M. F. & Marshall, C. J. Cross-talk between Ras and Rho signalling pathways in transformation favours proliferation and increased motility. Embo J 20, 755-66 (2001).
[1] Montell, D. J. Border-cell migration: the race is on. Nat Rev Mol Cell Biol 4, 13-24 (2003).
[2] Montell, D. J. The genetics of cell migration in Drosophila melanogaster and Caenorhabditis elegans development. Development 126,3035-46 (1999).
[3] Gilbert, S. F. The morphogenesis of evolutionary developmental biology. Int J Dev Biol 47,467-77 (2003).
[4] Keller, R. Cell migration during gastrulation. Curr Opin Cell Biol 17, 533-41 (2005).
[5] Lehmann, R. Cell migration in invertebrates: clues from border and distal tip cells. Curr Opin Genet Dev 11,457-63 (2001).
[6] Locascio, A. & Nieto, M. A. Cell movements during vertebrate development: integrated tissue behaviour versus individual cell migration. Curr Opin Genet Dev 11,464-9(2001).
[7] Marin, O. & Rubenstein, J. L. A long, remarkable journey: tangential migration in the telencephalon. Nat Rev Neurosci 2, 780-90 (2001).
[8] Brown, H. O., Levine, M. L. & Lipkin, M. Inhibition of intestinal epithelial cell renewal and migration induced by starvation. Am J Physiol 205, 868-72 (1963).
[9] Kunz, J. Proliferation, migration and cell renewal within the arterial wall. Acta Histochem Suppl 27,233-43 (1983).
[10] Decombas, M., Bonifay, P. & Kaqueler, J. C. [The role of hypocalcemia on cell renewal and migration in the oral epithelium of the rat]. J Biol Buccale 5, 245-59 (1977).
[11] Hattori, T. & Fujita, S. Tritiated thymidine autoradiographic study of cell migration and renewal in the pyloric mucosa of golden hamsters. Cell Tissue Res 175, 49-57 (1976).
[12] Stokowski, A., Shi, S., Sun, T., Bartold, P. M., Koblar, S. A. & Gronthos, S. EphB/ephrin-B interaction mediates adult stem cell attachment, spreading, and migration: implications for dental tissue repair. Stem Cells 25,156-64 (2007).
[13] Christensen, S. T., Pedersen, S. F., Satir, P., Veland, I. R. & Schneider, L. The primary cilium coordinates signaling pathways in cell cycle control and migration during development and tissue repair. Curr Top Dev Biol 85, 261-301 (2008).
[14] Pinco, K. A., He, W. & Yang, J. T. alpha4betal integrin regulates lamellipodia protrusion via a focal complex/focal adhesion-independent mechanism. Mol Biol Cell 13, 3203-17 (2002).
[15] Szekanecz, Z. & Koch, A. E. Cell-cell interactions in synovitis. Endothelial cells and immune cell migration. Arthritis Res 2, 368-73 (2000).
[16] Stachowiak, A. N. & Irvine, D. J. Inverse opal hydrogel-collagen composite scaffolds as a supportive microenvironment for immune cell migration. J Biomed Mater Res A 85, 815-28 (2008).
[17] Vicente-Manzanares, M., Sancho, D., Yanez-Mo, M. & Sanchez-Madrid, F. The leukocyte cytoskeleton in cell migration and immune interactions. Int Rev Cytol 216,233-89 (2002).
[18] Xiong, Y., Cao, C, Makarova, A., Hyman, B. & Zhang, L. Mac-1 promotes FcgammaRIIA-dependent cell spreading and migration on immune complexes. Biochemistry 45, 8721-31 (2006).
[19] Wang, H. W., Tedla, N., Lloyd, A. R., Wakefield, D. & McNeil, P. H. Mast cell activation and migration to lymph nodes during induction of an immune response in mice. J Clin Invest 102,1617-26 (1998).
[20] Westerberg, L., Larsson, M., Hardy, S. J., Fernandez, C, Thrasher, A. J. & Severinson, E. Wiskott-Aldrich syndrome protein deficiency leads to reduced B-cell adhesion, migration, and homing, and a delayed humoral immune response. Blood 105,1144-52 (2005).
[21] Luster, A. D., Alon, R. & von Andrian, U. H. Immune cell migration in inflammation: present and future therapeutic targets. Nat Immunol 6, 1182-90 (2005).
[22] Jones, G. E. Cellular signaling in macrophage migration and chemotaxis. J Leukoc Biol 68, 593-602 (2000).
[23] Kinashi, T. & Katagiri, K. Regulation of immune cell adhesion and migration by regulator of adhesion and cell polarization enriched in lymphoid tissues. Immunology 116, 164-71 (2005).
[24] Raines, E. W. The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease. Int J Exp Pathol 81, 173-82(2000).
[25] Cheong, A., Wood, I. C. & Beech, D. J. Less REST, more vascular disease? Regulation of cell cycle and migration of vascular smooth muscle cells. Cell Cycle 5,129-31(2006).
[26] Roque, M., Reis, E. D. & Roig, E. Role of smooth muscle cell migration and proliferation in allograft vascular disease. Transplant Proc 34, 333-4 (2002).
[27] McCarty, M. F. Thalidomide may impede cell migration in primates by down-regulating integrin beta-chains: potential therapeutic utility in solid malignancies, proliferative retinopathy, inflammatory disorders, neointimal hyperplasia, and osteoporosis. Med Hypotheses 49,123-31 (1997).
[28] Desmetz, C., Lin, Y. L., Mettling, C., Portales, P., Noel, D., Clot, J., Jorgensen, C. & Corbeau, P. Cell surface CCR5 density determines the intensity of T cell migration towards rheumatoid arthritis synoviocytes. Clin Immunol 123, 148-54 (2007).
[29] Woods, J. M., Klosowska, K., Spoden, D. J., Stumbo, N. G., Paige, D. J., Scatizzi, J. C., Volin, M. V., Rao, M. S. & Perlman, H. A cell-cycle independent role for p21 in regulating synovial fibroblast migration in rheumatoid arthritis. Arthritis Res Ther 8, R113 (2006).
[30] Ingegnoli, F., Blades, M., Manzo, A., Wahid, S., Perretti, M., Panayi, G. & Pitzalis, C. [Role of cell migration in the pathogenesis of rheumatoid arthritis: in vivo studies in SCID mice transplanted with human synovial membrane]. Reumatismo 54, 128-32 (2002).
[31] Mclnnes, I. B., al-Mughales, J., Field, M., Leung, B. P., Huang, F. P., Dixon, R., Sturrock, R. D., Wilkinson, P. C. & Liew, F. Y. The role of interleukin-15 in T-cell migration and activation in rheumatoid arthritis. Nat Med 2, 175-82 (1996).
[32] Zang, Y. C., Samanta, A. K., Haider, J. B., Hong, J., Tejada-Simon, M. V., Rivera, V. M. & Zhang, J. Z. Aberrant T cell migration toward RANTES and MIP-1 alpha in patients with multiple sclerosis. Overexpression of chemokine receptor CCR5. Brain 123 (Pt 9), 1874-82 (2000).
[33] Marracci, G. H., McKeon, G. P., Marquardt, W. E., Winter, R. W., Riscoe, M. K. & Bourdette, D. N. Alpha lipoic acid inhibits human T-cell migration: implications for multiple sclerosis. J Neurosci Res 78, 362-70 (2004).
[34] Dressel, A., Mirowska-Guzel, D., Gerlach, C. & Weber, F. Migration of T-cell subsets in multiple sclerosis and the effect of interferon-betala. Acta Neurol Scand 116, 164-8(2007).
[35] Tischner, D., Weishaupt, A., van den Brandt, J., Muller, N., Beyersdorf, N., Ip, C. W., Toyka, K. V., Hunig, T., Gold, R., Kerkau, T. & Reichardt, H. M. Polyclonal expansion of regulatory T cells interferes with effector cell migration in a model of multiple sclerosis. Brain 129,2635-47 (2006).
[36] Sinha, S., Subramanian, S., Proctor, T. M., Kaler, L. J., Grafe, M., Dahan, R., Huan, J., Vandenbark, A. A., Burrows, G. G. & Offher, H. A promising therapeutic approach for multiple sclerosis: recombinant T-cell receptor ligands modulate experimental autoimmune encephalomyelitis by reducing interleukin-17 production and inhibiting migration of encephalitogenic cells into the CNS. J Neurosci 27, 12531-9 (2007).
[37] Milner, R. Understanding the molecular basis of cell migration; implications for clinical therapy in multiple sclerosis. Clin Sci (Lond) 92, 113-22 (1997).
[38] Yamaguchi, H., Wyckoff, J. & Condeelis, J. Cell migration in tumors. Curr Opin Cell Biol 17, 559-64 (2005).
[39] Wang, W., Goswami, S., Sahai, E., Wyckoff, J. B., Segall, J. E. & Condeelis, J. S. Tumor cells caught in the act of invading: their strategy for enhanced cell motility. Trends Cell Biol 15, 138-45 (2005).
[40] Kerjan, G. & Gleeson, J. G. Moving neurons back into place. Nat Med 15, 17-8(2009).
[41] Kreis, P. & Barnier, J. V. PAK signalling in neuronal physiology. Cell Signal 21, 384-93 (2009).
[42] Lauffenburger, D. A. & Horwitz, A. F. Cell migration: a physically integrated molecular process. Cell 84, 359-69 (1996).
[43] Sheetz, M. P., Felsenfeld, D., Galbraith, C. G. & Choquet, D. Cell migration as a five-step cycle. Biochem Soc Symp 65, 233-43 (1999).
[44] Ridley, A. J., Schwartz, M. A., Burridge, K., Firtel, R. A., Ginsberg, M. H., Borisy, G., Parsons, J. T. & Horwitz, A. R. Cell migration: integrating signals from front to back. Science 302, 1704-9 (2003).
[45] Huang, C., Jacobson, K. & Schaller, M. D. MAP kinases and cell migration. J Cell Sci 117,4619-28(2004).
[46] Knight, B., Laukaitis, C, Akhtar, N., Hotchin, N. A., Edlund, M. & Horwitz, A. R. Visualizing muscle cell migration in situ. Curr Biol 10, 576-85 (2000).
[47] Friedl, P. & Wolf, K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3, 362-74 (2003).
[48] Pollard, T. D. & Borisy, G. G. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112,453-65 (2003).
[49] Koestler, S. A., Auinger, S., Vinzenz, M., Rottner, K. & Small, J. V. Differentially oriented populations of actin filaments generated in lamellipodia collaborate in pushing and pausing at the cell front. Nat Cell Biol 10, 306-13 (2008).
[50] Nemethova, M., Auinger, S. & Small, J. V. Building the actin cytoskeleton: filopodia contribute to the construction of contractile bundles in the lamella. J Cell Biol 180, 1233-44(2008).
[51] dos Remedios, C. G., Chhabra, D., Kekic, M., Dedova, I. V., Tsubakihara, M., Berry, D. A. & Nosworthy, N. J. Actin binding proteins: regulation of cytoskeletal microfilaments. Physiol Rev 83, 433-73 (2003).
[52] Akin, O. & Mullins, R. D. Capping protein increases the rate of actin-based motility by promoting filament nucleation by the Arp2/3 complex. Cell 133, 841-51 (2008).
[53] Etienne-Manneville, S. & Hall, A. Rho GTPases in cell biology. Nature 420, 629-35 (2002).
[54] Cory, G. O. & Ridley, A. J. Cell motility: braking WAVEs. Nature 418, 732-3 (2002).
[55] Snapper, S. B., Takeshima, F., Anton, I., Liu, C. H., Thomas, S. M., Nguyen, D., Dudley, D., Fraser, H., Purich, D., Lopez-Ilasaca, M., Klein, C, Davidson, L., Bronson, R., Mulligan, R. C., Southwick, F., Geha, R., Goldberg, M. B., Rosen, F. S., Hartwig, J. H. & Alt, F. W. N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility. Nat Cell Biol 3, 897-904 (2001).
[56] Katoh, H. & Negishi, M. RhoG activates Racl by direct interaction with the Dock180-binding protein Elmo. Nature 424, 461-4 (2003).
[57] Soderling, S. H., Binns, K. L., Wayman, G. A., Davee, S. M., Ong, S. H., Pawson, T. & Scott, J. D. The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling. Nat Cell Biol 4, 970-5 (2002).
[58] Cory, G. O., Garg, R., Cramer, R. & Ridley, A. J. Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome protein. J Biol Chem 277, 45115-21(2002).
[59] Hussain, N. K., Jenna, S., Glogauer, M., Quinn, C. C., Wasiak, S., Guipponi, M., Antonarakis, S. E., Kay, B. K., Stossel, T. P., Lamarche-Vane, N. & McPherson, P. S. Endocytic protein intersectin-1 regulates actin assembly via Cdc42 and N-WASP. Nat Cell Biol 3, 927-32 (2001).
[60] Suetsugu, S., Hattori, M., Miki, H., Tezuka, T., Yamamoto, T., Mikoshiba, K. & Takenawa, T. Sustained activation of N-WASP through phosphorylation is essential for neurite extension. Dev Cell 3, 645-58 (2002).
[61] Moreau, V., Frischknecht, F., Reckmann, I., Vincentelli, R., Rabut, G., Stewart, D. & Way, M. A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization. Nat Cell Biol 2, 441-8 (2000).
[62] Sasahara, Y., Rachid, R., Byrne, M. J., de la Fuente, M. A., Abraham, R. T., Ramesh, N. & Geha, R. S. Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation. Mol Cell 10, 1269-81 (2002).
[63] Itoh, R. E., Kurokawa, K., Ohba, Y., Yoshizaki, H., Mochizuki, N. & Matsuda, M. Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells. Mol Cell Biol 22, 6582-91 (2002).
[64] Srinivasan, S., Wang, F., Glavas, S., Ott, A., Hofmann, F., Aktories, K., Kalman, D. & Bourne, H. R. Rac and Cdc42 play distinct roles in regulating PI(3,4,5)P3 and polarity during neutrophil chemotaxis. J Cell Biol 160, 375-85 (2003).
[65] Rodriguez, O. C., Schaefer, A. W., Mandato, C. A., Forscher, P., Bement, W. M. & Waterman-Storer, C. M. Conserved microtubule-actin interactions in cell movement and morphogenesis. Nat Cell Biol 5, 599-609 (2003).
[66] Serrador, J. M., Nieto, M. & Sanchez-Madrid, F. Cytoskeletal rearrangement during migration and activation of T lymphocytes. Trends Cell Biol 9, 228-33 (1999).
[67] Etienne-Manneville, S. & Hall, A. Cell polarity: Par6, aPKC and cytoskeletal crosstalk. Curr Opin Cell Biol 15, 67-72 (2003).
[68] Li, Z., Hannigan, M., Mo, Z., Liu, B., Lu, W., Wu, Y., Smrcka, A. V., Wu, G., Li, L., Liu, M., Huang, C. K. & Wu, D. Directional sensing requires G beta gamma-mediated PAK1 and PIX alpha-dependent activation of Cdc42. Cell 114,215-27(2003).
[69] Etienne-Manneville, S. & Hall, A. Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. Cell 106, 489-98 (2001).
[70] Devreotes, P. & Janetopoulos, C. Eukaryotic chemotaxis: distinctions between directional sensing and polarization. J Biol Chem 278, 20445-8 (2003).
[71] Merlot, S. & Firtel, R. A. Leading the way: Directional sensing through phosphatidylinositol 3-kinase and other signaling pathways. J Cell Sci 116, 3471-8(2003).
[72] Welch, H. C., Coadwell, W. J., Stephens, L. R. & Hawkins, P. T. Phosphoinositide 3-kinase-dependent activation of Rac. FEBS Lett 546, 93-7 (2003).
[73] del Pozo, M. A., Price, L. S., Alderson, N. B., Ren, X. D. & Schwartz, M. A. Adhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK. Embo J 19, 2008-14 (2000).
[74] Kiosses, W. B., Shattil, S. J., Pampori, N. & Schwartz, M. A. Rac recruits high-affinity integrin alphavbeta3 to lamellipodia in endothelial cell migration. Nat Cell Biol 3, 316-20 (2001).
[75] Schwartz, M. A. & Shattil, S. J. Signaling networks linking integrins and rho family GTPases. Trends Biochem Sci 25, 388-91 (2000).
[76] Shattil, S. J. Function and regulation of the beta 3 integrins in hemostasis and vascular biology. Thromb Haemost 74, 149-55 (1995).
[77] Small, J. V. & Kaverina, I. Microtubules meet substrate adhesions to arrange cell polarity. Curr Opin Cell Biol 15,40-7 (2003).
[78] Evers, E. E., Zondag, G. C., Malliri, A., Price, L. S., ten Klooster, J. P., van der Kammen, R. A. & Collard, J. G. Rho family proteins in cell adhesion and cell migration. Eur J Cancer 36,1269-74 (2000).
[79] Worthylake, R. A. & Burridge, K. RhoA and ROCK promote migration by limiting membrane protrusions. J Biol Chem 278, 13578-84 (2003).
[80] Xu, J., Wang, F., Van Keymeulen, A., Herzmark, P., Straight, A., Kelly, K. Takuwa, Y., Sugimoto, N., Mitchison, T. & Bourne, H. R. Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell 114,201-14(2003).
[81] Gardiner, E. M., Pestonjamasp, K. N., Bohl, B. P., Chamberlain, C., Hahn, K. M. & Bokoch, G. M. Spatial and temporal analysis of Rac activation during live neutrophil chemotaxis. Curr Biol 12,2029-34 (2002).
[82] Tsuji, T., Ishizaki, T., Okamoto, M., Higashida, C., Kimura, K., Furuyashiki, T., Arakawa, Y., Birge, R. B., Nakamoto, T., Hirai, H. & Narumiya, S. ROCK and mDial antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts. J Cell Biol 157, 819-30 (2002).
[83] Geiger, B., Bershadsky, A., Pankov, R. & Yamada, K. M. Transmembrane crosstalk between the extracellular matrix-cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2, 793-805 (2001).
[84] Emsley, J., Knight, C. G., Farndale, R. W., Barnes, M. J. & Liddington, R. C. Structural basis of collagen recognition by integrin alpha2betal. Cell 101, 47-56 (2000).
[85] Kim, M., Carman, C. V. & Springer, T. A. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 301, 1720-5 (2003).
[86] Kinbara, K., Goldfinger, L. E., Hansen, M., Chou, F. L. & Ginsberg, M. H. Ras GTPases: integrins' friends or foes? Nat Rev Mol Cell Biol 4, 767-76 (2003).
[87] Tadokoro, S., Shattil, S. J., Eto, K., Tai, V., Liddington, R. C, de Pereda, J. M., Ginsberg, M. H. & Calderwood, D. A. Talin binding to integrin beta tails: a final common step in integrin activation. Science 302, 103-6 (2003).
[88] Goldfinger, L. E., Han, J., Kiosses, W. B., Howe, A. K. & Ginsberg, M. H. Spatial restriction of alpha4 integrin phosphorylation regulates lamellipodial stability and alpha4betal-dependent cell migration. J Cell Biol 162, 731-41 (2003).
[89] Webb, D. J., Parsons, J. T. & Horwitz, A. F. Adhesion assembly, disassembly and turnover in migrating cells - over and over and over again. Nat Cell Biol 4,E97-100(2002).
[90] Beningo, K. A., Dembo, M, Kaverina, I., Small, J. V. & Wang, Y. L. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J Cell Biol 153, 881-8 (2001).
[91] Galbraith, C. G., Yamada, K. M. & Sheetz, M. P. The relationship between force and focal complex development. J Cell Biol 159, 695-705 (2002).
[92] Riento, K. & Ridley, A. J. Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 4,446-56 (2003).
[93] Balaban, N. Q., Schwarz, U. S., Riveline, D., Goichberg, P., Tzur, G., Sabanay, I., Mahalu, D., Safran, S., Bershadsky, A., Addadi, L. & Geiger, B. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat Cell Biol 3,466-72 (2001).
[94] Larsen, M., Tremblay, M. L. & Yamada, K. M. Phosphatases in cell-matrix adhesion and migration. Nat Rev Mol Cell Biol 4, 700-11 (2003).
[95] Alahari, S. K., Reddig, P. J. & Juliano, R. L. Biological aspects of signal transduction by cell adhesion receptors. Int Rev Cytol 220, 145-84 (2002).
[96] Turner, C. E., West, K. A. & Brown, M. C. Paxillin-ARF GAP signaling and the cytoskeleton. Curr Opin Cell Biol 13, 593-9 (2001).
[97] Brahmbhatt, A. A. & Klemke, R. L. ERK and RhoA differentially regulate pseudopodia growth and retraction during chemotaxis. J Biol Chem 278, 13016-25 (2003).
[98] Chung, C. Y., Potikyan, G. & Firtel, R. A. Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa. Mol Cell 7, 937-47 (2001).
[99] Lee, J., Ishihara, A., Oxford, G., Johnson, B. & Jacobson, K. Regulation of cell movement is mediated by stretch-activated calcium channels. Nature 400, 382-6 (1999).
[100] Glading, A., Lauffenburger, D. A. & Wells, A. Cutting to the chase: calpain proteases in cell motility. Trends Cell Biol 12,46-54 (2002).
[101] Ridley, A. J. Rho GTPases and cell migration. J Cell Sci 114, 2713-22 (2001).
[102] Webb, D. J., Donais, K., Whitmore, L. A., Thomas, S. M., Turner, C. E., Parsons, J. T. & Horwitz, A. F. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol 6, 154-61 (2004).
[103] Hood, J. D. & Cheresh, D. A. Role of integrins in cell invasion and migration. Nat Rev Cancer 2, 91-100 (2002).
[104] Howe, A. K. & Juliano, R. L. Regulation of anchorage-dependent signal transduction by protein kinase A and p21-activated kinase. Nat Cell Biol 2, 593-600 (2000).
[105] Weaver, A. M., Young, M. E., Lee, W. L. & Cooper, J. A. Integration of signals to the Arp2/3 complex. Curr Opin Cell Biol 15,23-30 (2003).
[106] Vartiainen, M. K. & Machesky, L. M. The WASP-Arp2/3 pathway: genetic insights. Curr Opin Cell Biol 16, 174-81 (2004).
[107] Watanabe, N. & Higashida, C. Formins: processive cappers of growing actin filaments. Exp Cell Res 301, 16-22 (2004).
[108] Krause, M., Dent, E. W., Bear, J. E., Loureiro, J. J. & Gertler, F. B. Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration. Annu Rev Cell Dev Biol 19, 541-64 (2003).
[109] Jaffe, A. B. & Hall, A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21,247-69 (2005).
[110] Wittmann, T., Bokoch, G. M. & Waterman-Storer, C. M. Regulation of microtubule destabilizing activity of Op18/stathmin downstream of Racl. J Biol Chem 279, 6196-203 (2004).
[111] Gomes, E. R., Jani, S. & Gundersen, G. G. Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Cell 121, 451-63 (2005).
[112] Ezratty, E. J., Partridge, M. A. & Gundersen, G. G. Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol 7, 581-90 (2005).
[113] Franco, S. J., Rodgers, M. A., Perrin, B. J., Han, J., Bennin, D. A., Critchley, D. R. & Huttenlocher, A. Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nat Cell Biol 6, 977-83 (2004).
[114] Olson, M. F. & Sahai, E. The actin cytoskeleton in cancer cell motility. Clin Exp Metastasis 26, 273-87 (2009).
[115] Brooks, S. A., Lomax-Browne, H. J., Carter, T. M., Kinch, C. E. & Hall, D. M. Molecular interactions in cancer cell metastasis. Acta Histochem (2009).
[116] Chiang, A. C. & Massague, J. Molecular basis of metastasis. N Engl J Med 359,2814-23(2008).