Focal adhesion kinase: in command and control of cell motility (original) (raw)

• Brakebusch, C. & Fassler, R. The integrin–actin connection, an eternal love affair. EMBO J. 22, 2324–2333 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• DeMali, K. A., Wennerberg, K. & Burridge, K. Integrin signaling to the actin cytoskeleton. Curr. Opin. Cell Biol. 15, 572–582 (2003).
  Article CAS PubMed Google Scholar
• Ridley, A. J. et al. Cell migration: integrating signals from front to back. Science 302, 1704–1709 (2003).
  Article CAS PubMed Google Scholar
• Parsons, J. T. Focal adhesion kinase: the first ten years. J. Cell Sci. 116, 1409–1416 (2003). Provides a good overview of the early studies on FAK.
  Article CAS PubMed Google Scholar
• Ilic, D. et al. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377, 539–544 (1995). Shows that null mutation of FAK results in defects in embryonic morphogenesis, and that FAK-null cells show enhanced focal-contact formation and cell motility defects in culture.
  Article CAS PubMed Google Scholar
• Webb, D. J. et al. FAK–Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nature Cell Biol. 6, 154–161 (2004).
  Article CAS PubMed Google Scholar
• Palazzo, A. F., Eng, C. H., Schlaepfer, D. D., Marcantonio, E. E. & Gundersen, G. G. Localized stabilization of microtubules by integrin- and FAK-facilitated Rho signaling. Science 303, 836–839 (2004). Provides evidence that FAK promotes cell polarization through the stabilization of microtubules at leading edges of motile cells.
  Article CAS PubMed Google Scholar
• Ren, X. et al. Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. J. Cell Sci. 113, 3673–3678 (2000).
  Article CAS PubMed Google Scholar
• Agochiya, M. et al. Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells. Oncogene 18, 5646–5653 (1999).
  Article CAS PubMed Google Scholar
• Bhattacharjee, A. et al. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc. Natl Acad. Sci. USA 98, 13790–13795 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Yeoh, E. J. et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 1, 133–143 (2002).
  Article CAS PubMed Google Scholar
• Cance, W. G. et al. Immunohistochemical analyses of focal adhesion kinase expression in benign and malignant human breast and colon tissues: correlation with preinvasive and invasive phenotypes. Clin. Cancer Res. 6, 2417–2423 (2000).
  CAS PubMed Google Scholar
• Ilic, D. et al. Focal adhesion kinase is required for blood vessel morphogenesis. Circ. Res. 92, 300–307 (2003).
  Article CAS PubMed Google Scholar
• Haskell, H. et al. Focal adhesion kinase is expressed in the angiogenic blood vessels of malignant astrocytic tumors in vivo and promotes capillary tube formation of brain microvascular endothelial cells. Clin. Cancer Res. 9, 2157–2165 (2003).
  CAS PubMed Google Scholar
• Hauck, C. R., Hsia, D. A., Ilic, D. & Schlaepfer, D. D. v-Src SH3-enhanced interaction with focal adhesion kinase at β1 integrin-containing invadopodia promotes cell invasion. J. Biol. Chem. 277, 12487–12490 (2002).
  Article CAS PubMed Google Scholar
• Hauck, C. R., Hsia, D. A., Puente, X. S., Cheresh, D. A. & Schlaepfer, D. D. FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth. EMBO J. 21, 6289–6302 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Hsia, D. A. et al. Differential regulation of cell motility and invasion by FAK. J. Cell Biol. 160, 753–767 (2003). This reference, together with reference 69, shows that constitutively active Src can bypass the need for FAK in promoting the turnover of focal contacts.
  Article CAS PubMed PubMed Central Google Scholar
• Schlaepfer, D. D., Mitra, S. K. & Ilic, D. Control of motile and invasive cell phenotypes by focal adhesion kinase. Biochim. Biophys. Acta 1692, 77–102 (2004). Provides a solid review on the role of FAK during embryonic development.
  Article CAS PubMed Google Scholar
• Yano, H. et al. Roles played by a subset of integrin signaling molecules in cadherin-based cell–cell adhesion. J. Cell Biol. 166, 283–295 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Katsumi, A., Orr, A. W., Tzima, E. & Schwartz, M. A. Integrins in mechanotransduction. J. Biol. Chem. 279, 12001–12004 (2004).
  Article CAS PubMed Google Scholar
• 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, 1442–1450 (2003).
  Article CAS PubMed Google Scholar
• Hauck, C. R. et al. Inhibition of focal adhesion kinase expression or activity disrupts epidermal growth factor-stimulated signaling promoting the migration of invasive human carcinoma cells. Cancer Res. 61, 7079–7090 (2001).
  CAS PubMed Google Scholar
• Sieg, D. J. et al. FAK integrates growth-factor and integrin signals to promote cell migration. Nature Cell Biol. 2, 249–256 (2000).
  Article CAS PubMed Google Scholar
• Streblow, D. N. et al. Human cytomegalovirus chemokine receptor US28-induced smooth muscle cell migration is mediated by focal adhesion kinase and Src. J. Biol. Chem. 278, 50456–50465 (2003). Together with reference 23, this paper shows that the FAK FERM domain has important roles in promoting growth-factor-stimulated and G-protein-stimulated cell motility.
  Article CAS PubMed Google Scholar
• Chen, R. et al. Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain. Nature Cell Biol. 3, 439–444 (2001).
  Article CAS PubMed Google Scholar
• Poullet, P. et al. Ezrin interacts with focal adhesion kinase and induces its activation independently of cell–matrix adhesion. J. Biol. Chem. 276, 37686–37691 (2001).
  Article CAS PubMed Google Scholar
• Kadare, G. et al. PIAS1-mediated sumoylation of focal adhesion kinase activates its autophosphorylation. J. Biol. Chem. 278, 47434–47440 (2003). Shows that sumoylation of FAK within the FERM domain is associated with catalytic activation and preferential nuclear localization.
  Article CAS PubMed Google Scholar
• Jones, G. & Stewart, G. Nuclear import of N-terminal FAK by activation of the FcεRI receptor in RBL-2H3 cells. Biochem. Biophys. Res. Comm. 314, 39–45 (2004).
  Article CAS PubMed Google Scholar
• McKean, D. M. et al. FAK induces expression of Prx1 to promote tenascin-C-dependent fibroblast migration. J. Cell Biol. 161, 393–402 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Zhao, J. et al. Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression. Mol. Cell 11, 1503–1515 (2003).
  Article CAS PubMed Google Scholar
• Hanks, S. K., Ryzhova, L., Shin, N. Y. & Brabek, J. Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility. Front. Biosci. 8, 982–996 (2003).
  Article Google Scholar
• Chodniewicz, D. & Klemke, R. L. Regulation of integrin-mediated cellular responses through assembly of a CAS/Crk scaffold. Biochim. Biophys. Acta. 1692, 63–76 (2004).
  Article CAS PubMed Google Scholar
• Schaller, M. D. Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim. Biophys. Acta. 1540, 1–21 (2001).
  Article CAS PubMed Google Scholar
• Zhai, J. et al. Direct interaction of focal adhesion kinase with p190RhoGEF. J. Biol. Chem. 278, 24865–24873 (2003). Together with reference 79, shows that FAK can directly activate Rho through binding and phosphorylation of a GEF, and that this activation regulates axonal branching.
  Article CAS PubMed Google Scholar
• Toutant, M. et al. Alternative splicing controls the mechanisms of FAK autophosphorylation. Mol. Cell. Biol. 22, 7731–7743 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Liu, E., Cote, J. F. & Vuori, K. Negative regulation of FAK signaling by SOCS proteins. EMBO J. 22, 5036–5046 (2003). This paper established a link between FAK activation, phosphorylation of Tyr397 and subsequent degradation of FAK.
  Article CAS PubMed PubMed Central Google Scholar
• Avraham, H., Park, S. Y., Schinkmann, K. & Avraham, S. RAFTK/Pyk2-mediated cellular signalling. Cell. Signal 12, 123–133 (2000).
  Article CAS PubMed Google Scholar
• Klingbeil, C. K. et al. Targeting Pyk2 to β1-integrin-containing focal contacts rescues fibronectin-stimulated signaling and haptotactic motility defects of focal adhesion kinase-null cells. J. Cell Biol. 152, 97–110 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Lim, Y. et al. Phosphorylation of focal adhesion kinase at tyrosine 861 is crucial for Ras transformation of fibroblasts. J. Biol. Chem. 279, 29060–29065 (2004).
  Article CAS PubMed Google Scholar
• Gabarra-Niecko, V., Keely, P. J. & Schaller, M. D. Characterization of an activated mutant of focal adhesion kinase: 'SuperFAK'. Biochem. J. 365, 591–603 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Nowakowski, J. et al. Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography. Structure (Camb.) 10, 1659–1667 (2002).
  Article CAS Google Scholar
• Abbi, S. et al. Regulation of focal adhesion kinase by a novel protein inhibitor FIP200. Mol. Biol. Cell 13, 3178–3191 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Medley, Q. G. et al. Signaling between focal adhesion kinase and Trio. J. Biol. Chem. 278, 13265–13270 (2003).
  Article CAS PubMed Google Scholar
• Cooper, L. A., Shen, T. L. & Guan, J. L. Regulation of focal adhesion kinase by its amino-terminal domain through an autoinhibitory interaction. Mol. Cell. Biol. 23, 8030–8041 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Zeng, L. et al. PTPα regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration. J. Cell Biol. 160, 137–146 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Chiarugi, P. et al. Reactive oxygen species as essential mediators of cell adhesion: the oxidative inhibition of a FAK tyrosine phosphatase is required for cell adhesion. J. Cell Biol. 161, 933–944 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Arias-Salgado, E. G. et al. Src kinase activation by direct interaction with the integrin β cytoplasmic domain. Proc. Natl Acad. Sci. USA 100, 13298–13302 (2003). Shows that selected β-integrin subunits can bind and activate Src in the absence of a contribution from FAK.
  Article CAS PubMed PubMed Central Google Scholar
• Turner, C. E. Paxillin and focal adhesion signalling. Nature Cell Biol. 2, 231–236 (2000).
  Article CAS Google Scholar
• Cho, S. Y. & Klemke, R. L. Purification of pseudopodia from polarized cells reveals redistribution and activation of Rac through assembly of a CAS/Crk scaffold. J. Cell Biol. 156, 725–736 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Brabek, J. et al. CAS promotes invasiveness of Src-transformed cells. Oncogene 23, 7406–7415 (2004).
  Article CAS PubMed Google Scholar
• Schaller, M. D. Paxillin: a focal adhesion-associated adaptor protein. Oncogene 20, 6459–6472 (2001).
  Article CAS PubMed Google Scholar
• Subauste, M. C. et al. Vinculin modulation of paxillin–FAK interactions regulates ERK to control survival and motility. J. Cell Biol. 165, 371–381 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Hayashi, I., Vuori, K. & Liddington, R. C. The focal adhesion targeting (FAT) region of focal adhesion kinase is a four-helix bundle that binds paxillin. Nature Struct. Biol. 9, 101–106 (2002).
  Article CAS PubMed Google Scholar
• Liu, G., Guibao, C. D. & Zheng, J. Structural insight into the mechanisms of targeting and signaling of focal adhesion kinase. Mol. Cell. Biol. 22, 2751–2760 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Gao, G. et al. NMR solution structure of the focal adhesion targeting domain of focal adhesion kinase in complex with a paxillin LD peptide: evidence for a two-site binding model. J. Biol. Chem. 279, 8441–8451 (2004).
  Article CAS PubMed Google Scholar
• Katz, B. Z. et al. Targeting membrane-localized focal adhesion kinase to focal adhesions: roles of tyrosine phosphorylation and SRC family kinases. J. Biol. Chem. 278, 29115–29120 (2003).
  Article CAS PubMed Google Scholar
• Prutzman, K. C. et al. The focal adhesion targeting domain of focal adhesion kinase contains a hinge region that modulates tyrosine 926 phosphorylation. Structure (Camb.) 12, 881–891 (2004). References 53, 54, 55 and 57 provide structural analyses of the FAK FAT domain and the paxillin LD peptide binding, and show that Tyr925 phosphorylation might require conformational alterations in the FAT domain.
  Article CAS Google Scholar
• Ma, A., Richardson, A., Schaefer, E. M. & Parsons, J. T. Serine phosphorylation of focal adhesion kinase in interphase and mitosis: a possible role in modulating binding to p130Cas. Mol. Biol. Cell 12, 1–12 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Hunger-Glaser, I., Fan, R. S., Perez-Salazar, E. & Rozengurt, E. PDGF and FGF induce focal adhesion kinase (FAK) phosphorylation at Ser-910: dissociation from Tyr-397 phosphorylation and requirement for ERK activation. J. Cell Physiol. 200, 213–222 (2004).
  Article CAS PubMed Google Scholar
• 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, 10452–10458 (2002).
  Article CAS PubMed Google Scholar
• Ishibe, S., Joly, D., Zhu, X. & Cantley, L. G. Phosphorylation-dependent paxillin–ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis. Mol. Cell 12, 1275–1285 (2003).
  Article CAS PubMed Google Scholar
• Kirchner, J., Kam, Z., Tzur, G., Bershadsky, A. D. & Geiger, B. Live-cell monitoring of tyrosine phosphorylation in focal adhesions following microtubule disruption. J. Cell Sci. 116, 975–986 (2003).
  Article CAS PubMed Google Scholar
• Zaidel-Bar, R., Ballestrem, C., Kam, Z. & Geiger, B. Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells. J. Cell Sci. 116, 4605–4613 (2003).
  Article CAS PubMed Google Scholar
• Sieg, D. J., Hauck, C. R. & Schlaepfer, D. D. Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration. J. Cell Sci. 112, 2677–2691 (1999).
  Article CAS PubMed Google Scholar
• Rajfur, Z., Roy, P., Otey, C., Romer, L. & Jacobson, K. Dissecting the link between stress fibres and focal adhesions by CALI with EGFP fusion proteins. Nature Cell Biol. 4, 286–293 (2002).
  Article CAS PubMed Google Scholar
• Izaguirre, G. et al. The cytoskeletal/non-muscle isoform of α-actinin is phosphorylated on its actin-binding domain by the focal adhesion kinase. J. Biol. Chem. 276, 28676–28685 (2001).
  Article CAS PubMed Google Scholar
• Yu, D. H., Qu, C. K., Henegariu, O., Lu, X. & Feng, G. S. Protein-tyrosine phosphatase Shp-2 regulates cell spreading, migration, and focal adhesion. J. Biol. Chem. 273, 21125–21131 (1998).
  Article CAS PubMed Google Scholar
• Von Wichert, G., Haimovich, B., Feng, G. S. & Sheetz, M. P. Force-dependent integrin–cytoskeleton linkage formation requires downregulation of focal complex dynamics by Shp2. EMBO J. 22, 5023–5035 (2003). Together with reference 67, this study shows that null mutation of SHP2 results in FAK hyperactivation, elevated α-actinin phosphorylation, and the failure to promote the maturation of integrin–cytoskeletal linkages.
  Article CAS PubMed PubMed Central Google Scholar
• Moissoglu, K. & Gelman, I. H. v-Src rescues actin-based cytoskeletal architecture and cell motility and induces enhanced anchorage independence during oncogenic transformation of focal adhesion kinase-null fibroblasts. J. Biol. Chem. 278, 47946–47959 (2003).
  Article CAS PubMed Google Scholar
• Visse, R. & Nagase, H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ. Res. 92, 827–839 (2003).
  Article CAS PubMed Google Scholar
• Bhatt, A., Kaverina, I., Otey, C. & Huttenlocher, A. Regulation of focal complex composition and disassembly by the calcium-dependent protease calpain. J. Cell Sci. 115, 3415–3425 (2002).
  Article CAS PubMed Google Scholar
• Dourdin, N. et al. Reduced cell migration and disruption of the actin cytoskeleton in calpain-deficient embryonic fibroblasts. J. Biol. Chem. 276, 48382–48388 (2001).
  Article CAS PubMed Google Scholar
• Cuevas, B. D. et al. MEKK1 regulates calpain-dependent proteolysis of focal adhesion proteins for rear-end detachment of migrating fibroblasts. EMBO J. 22, 3346–3355 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Westhoff, M. A., Serrels, B., Fincham, V. J., Frame, M. C. & Carragher, N. O. Src-mediated phosphorylation of focal adhesion kinase couples actin and adhesion dynamics to survival signaling. Mol. Cell. Biol. 24, 8113–8133 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Giannone, G. et al. Calcium rises locally trigger focal adhesion disassembly and enhance residency of focal adhesion kinase at focal adhesions. J. Biol. Chem. 279, 28715–28723 (2004).
  Article CAS PubMed Google Scholar
• Hecker, T. P., Ding, Q., Rege, T. A., Hanks, S. K. & Gladson, C. L. Overexpression of FAK promotes Ras activity through the formation of a FAK/p120RasGAP complex in malignant astrocytoma cells. Oncogene 23, 3962–3971 (2004).
  Article CAS PubMed Google Scholar
• Chen, B. H., Tzen, J. T., Bresnick, A. R. & Chen, H. C. Roles of Rho-associated kinase and myosin light chain kinase in morphological and migratory defects of focal adhesion kinase-null cells. J. Biol. Chem. 277, 33857–33863 (2002).
  Article CAS PubMed Google Scholar
• Arthur, W. T., Petch, L. A. & Burridge, K. Integrin engagement suppresses RhoA activity via a c-Src-dependent mechanism. Curr. Biol. 10, 719–722 (2000).
  Article CAS PubMed Google Scholar
• Rico, B. et al. Control of axonal branching and synapse formation by focal adhesion kinase. Nature Neurosci. 7, 1059–1069 (2004).
  Article CAS PubMed Google Scholar
• Wu, X., Suetsugu, S., Cooper, L. A., Takenawa, T. & Guan, J. L. Focal adhesion kinase regulation of N-WASP subcellular localization and function. J. Biol. Chem. 279, 9565–9576 (2004).
  Article CAS PubMed Google Scholar
• Palazzo, A. F., Cook, T. A., Alberts, A. S. & Gundersen, G. G. mDia mediates Rho-regulated formation and orientation of stable microtubules. Nature Cell Biol. 3, 723–729 (2001).
  Article CAS PubMed Google Scholar
• Gundersen, G. G., Gomes, E. R. & Wen, Y. Cortical control of microtubule stability and polarization. Curr. Opin. Cell Biol. 16, 106–112 (2004).
  Article CAS PubMed Google Scholar
• del Pozo, M. A. et al. Integrins regulate Rac targeting by internalization of membrane domains. Science 303, 839–842 (2004).
  Article CAS PubMed Google Scholar
• 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, 2008–2014 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Slack-Davis, J. K. et al. PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation. J. Cell Biol. 162, 281–291 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Xie, Z. et al. Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration. Cell 114, 469–482 (2003).
  Article CAS PubMed Google Scholar
• Ivankovic-Dikic, I., Gronroos, E., Blaukat, A., Barth, B. -U. & Dikic, I. Pyk2 and FAK regulate neurite outgrowth induced by growth factors and integrins. Nature Cell Biol. 2, 574–581 (2000).
  Article CAS PubMed Google Scholar
• Calderwood, D. A. Integrin activation. J. Cell Sci. 117, 657–666 (2004).
  Article CAS PubMed Google Scholar
• Papagrigoriou, E. et al. Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle. EMBO J. 23, 2942–2951 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Di Paolo, G. et al. Recruitment and regulation of phosphatidylinositol phosphate kinase type 1γ by the FERM domain of talin. Nature 420, 85–89 (2002).
  Article CAS PubMed Google Scholar
• Ling, K., Doughman, R. L., Firestone, A. J., Bunce, M. W. & Anderson, R. A. Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature 420, 89–93 (2002).
  Article CAS PubMed Google Scholar
• Barsukov, I. L. et al. Phosphatidylinositol phosphate kinase type 1γ and β1-integrin cytoplasmic domain bind to the same region in the talin FERM domain. J. Biol. Chem. 278, 31202–31209 (2003).
  Article CAS PubMed Google Scholar
• Ling, K. et al. Tyrosine phosphorylation of type Iγ phosphatidylinositol phosphate kinase by Src regulates an integrin–talin switch. J. Cell Biol. 163, 1339–1349 (2003). Together with references 91 and 92, this reference shows that FAK–Src phosphorylation events function to control the composition of membrane lipids and the dynamics of focal contacts.
  Article CAS PubMed PubMed Central Google Scholar
• Wheelock, M. J. & Johnson, K. R. Cadherins as modulators of cellular phenotype. Ann. Rev. Cell Dev. Biol. 19, 207–235 (2003).
  Article CAS Google Scholar
• Irby, R. B. & Yeatman, T. J. Increased Src activity disrupts cadherin/catenin-mediated homotypic adhesion in human colon cancer and transformed rodent cells. Cancer Res. 62, 2669–2674 (2002).
  CAS PubMed Google Scholar
• Avizienyte, E. et al. Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling. Nature Cell Biol. 4, 632–638 (2002).
  Article CAS PubMed Google Scholar
• Quadri, S. K., Bhattacharjee, M., Parthasarathi, K., Tanita, T. & Bhattacharya, J. Endothelial barrier strengthening by activation of focal adhesion kinase. J. Biol. Chem. 278, 13342–13349 (2003).
  Article CAS PubMed Google Scholar
• Miranti, C. K. & Brugge, J. S. Sensing the environment: a historical perspective on integrin signal transduction. Nature Cell Biol. 4, E83–E90 (2002).
  Article CAS PubMed Google Scholar
• Li, S. et al. The role of the dynamics of focal adhesion kinase in the mechanotaxis of endothelial cells. Proc. Natl Acad. Sci. USA 99, 3546–3551 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, H. B., Dembo, M., Hanks, S. K. & Wang, Y. Focal adhesion kinase is involved in mechanosensing during fibroblast migration. Proc. Natl Acad. Sci. USA 98, 11295–11300 (2001). Shows that FAK functions as an important environmental biosensor in promoting directional motility signals in response to changes in substrate flexibility.
  Article CAS PubMed PubMed Central Google Scholar
• Owen, J. D., Ruest, P. J., Fry, D. W. & Hanks, S. K. Induced focal adhesion kinase (FAK) expression in FAK-null cells enhances cell spreading and migration requiring both auto- and activation loop phosphorylation sites and inhibits adhesion-dependent tyrosine phosphorylation of Pyk2. Mol. Cell. Biol. 19, 4806–4818 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Cukierman, E., Pankov, R. & Yamada, K. M. Cell interactions with three-dimensional matrices. Curr. Opin. Cell Biol. 14, 633–639 (2002).
  Article CAS PubMed Google Scholar
• Ilic, D. et al. FAK promotes organization of fibronectin matrix and fibrillar adhesions. J. Cell Sci. 117, 177–187 (2004).
  Article CAS PubMed Google Scholar
• Beggs, H. E. et al. FAK deficiency in cells contributing to the basal lamina results in cortical abnormalities resembling congenital muscular dystrophies. Neuron 40, 501–514 (2003). References 103 and 104 show that FAK has crucial roles in promoting 3D-matrix assembly and/or remodelling during development and in cell culture model systems.
  Article CAS PubMed PubMed Central Google Scholar
• Cukierman, E., Pankov, R., Stevens, D. R. & Yamada, K. M. Taking cell–matrix adhesions to the third dimension. Science 294, 1708–1712 (2001).
  Article CAS PubMed Google Scholar
• Xia, H., Nho, R. S., Kahm, J., Kleidon, J. & Henke, C. A. Focal adhesion kinase is upstream of phosphatidylinositol 3-kinase/Akt in regulating fibroblast survival in response to contraction of type I collagen matrices via a β1 integrin viability signaling pathway. J. Biol. Chem. 279, 33024–33034 (2004).
  Article CAS PubMed Google Scholar
• Wozniak, M. A., Desai, R., Solski, P. A., Der, C. J. & Keely, P. J. ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix. J. Cell Biol. 163, 583–595 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Ilic, D. et al. Plasma membrane-associated pY397FAK is a marker of cytotrophoblast invasion in vivo and in vitro. Am. J. Pathol. 159, 93–108 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Bowden, E. T., Coopman, P. J. & Mueller, S. C. Invadopodia: unique methods for measurement of extracellular matrix degradation in vitro. Methods Cell Biol. 63, 613–627 (2001).
  Article CAS PubMed Google Scholar
• Hauck, C. R., Hunter, T. & Schlaepfer, D. D. The v-Src SH3 domain facilitates a cell adhesion-independent association with focal adhesion kinase. J. Biol. Chem. 276, 17653–17662 (2001).
  Article CAS PubMed Google Scholar
• Stewart, A., Ham, C. & Zachary, I. The focal adhesion kinase amino-terminal domain localises to nuclei and intercellular junctions in HEK 293 and MDCK cells independently of tyrosine 397 and the carboxy-terminal domain. Biochem. Biophys. Res. Comm. 299, 62–73 (2002).
  Article CAS PubMed Google Scholar
• Chen, H. C., Appeddu, P. A., Isoda, H. & Guan, J. L. Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase. J. Biol. Chem. 271, 26329–26334 (1996).
  Article CAS PubMed Google Scholar
• Calderwood, D. A. & Ginsberg, M. H. Talin forges the links between integrins and actin. Nature Cell Biol. 5, 694–697 (2003).
  Article CAS PubMed Google Scholar
• Zheng, C. et al. Differential regulation of Pyk2 and focal adhesion kinase (FAK). J. Biol. Chem. 273, 2384–2389 (1998).
  Article CAS PubMed Google Scholar
• Wang, Q. et al. Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin. J. Cell Biol. 160, 565–575 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Sieg, D. J. et al. Pyk2 and Src-family protein-tyrosine kinases compensate for the loss of FAK in fibronectin-stimulated signaling events but Pyk2 does not fully function to enhance FAK− cell migration. EMBO J. 17, 5933–5947 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Lakkakorpi, P. T., Bett, A. J., Lipfert, L., Rodan, G. A. & Duong, L. T. Pyk2 autophosphorylation, but not kinase activity, is necessary for adhesion-induced association with c-Src, osteoclast spreading, and bone resorption. J. Biol. Chem. 278, 11502–11512 (2003).
  Article CAS PubMed Google Scholar
• Lev, S. et al. Identification of a novel family of targets of Pyk2 related to Drosophila retinal degeneration B (rdgB) protein. Mol. Cell. Biol. 19, 2278–2288 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Benbernou, N., Muegge, K. & Durum, S. K. Interleukin (IL)-7 induces rapid activation of Pyk2, which is bound to Janus kinase 1 and IL-7Rα. J. Biol. Chem. 275, 7060–7065 (2000).
  Article CAS PubMed Google Scholar
• Okigaki, M. et al. Pyk2 regulates multiple signaling events crucial for macrophage morphology and migration. Proc. Natl Acad. Sci. USA 100, 10740–10745 (2003). Shows that null mutation of the FAK-related kinase PYK2 results in integrin and chemokine-stimulated motility defects of macrophages that are not functionally compensated by FAK expression.
  Article CAS PubMed PubMed Central Google Scholar
• Watson, J. M. et al. Inhibition of the calcium-dependent tyrosine kinase (CADTK) blocks monocyte spreading and motility. J. Biol. Chem. 276, 3536–3542 (2001).
  Article CAS PubMed Google Scholar
• Guinamard, R., Okigaki, M., Schlessinger, J. & Ravetch, J. V. Absence of marginal zone B cells in Pyk2-deficient mice defines their role in the humoral response. Nature Immunol. 1, 31–36 (2000).
  Article CAS Google Scholar
• Klinghoffer, R. A., Sachsenmaier, C., Cooper, J. A. & Soriano, P. Src family kinases are required for integrin but not PDGFR signal transduction. EMBO J. 18, 2459–2471 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Honda, H. et al. Cardiovascular anomaly, impaired actin bundling and resistance to Src- induced transformation in mice lacking p130Cas. Nature Genet. 19, 361–365 (1998).
  Article CAS PubMed Google Scholar
• Hagel, M. et al. The adaptor protein paxillin is essential for normal development in the mouse and is a critical transducer of fibronectin signaling. Mol. Cell. Biol. 22, 901–915 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Xu, W., Baribault, H. & Adamson, E. D. Vinculin knockout results in heart and brain defects during embryonic development. Development 125, 327–337 (1998).
  Article CAS PubMed Google Scholar