Focal adhesion kinase: In command and control of cell motility

Nature Reviews Molecular Cell Biology

Volumn 6, Issue 1, 2005, Pages 56-68

  Mitra, Satyajit K ^a   Hanson, Daniel A ^a   Schlaepfer, David D ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIN; ALPHA ACTININ; ALPHA INTEGRIN; BETA INTEGRIN; CADHERIN; CALPAIN; EPIDERMAL GROWTH FACTOR RECEPTOR; EZRIN; FOCAL ADHESION KINASE; G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; MYOSIN; PAXILLIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOLIPASE C; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN CDC42; PROTEIN P130; PROTEIN TYROSINE KINASE; RAC PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; SUMO PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING; TALIN; UNINDEXED DRUG; VINCULIN; ZYXIN;

AUTOPHOSPHORYLATION; BIOSENSOR; CELL ADHESION; CELL MEMBRANE; CELL MOTILITY; CELL MOTION; CELLULAR DISTRIBUTION; CYTOSKELETON; ENZYME ACTIVATION; ENZYME REGULATION; EXTRACELLULAR MATRIX; FILOPODIUM; HUMAN; LAMELLIPODIUM; MEMBRANE STRUCTURE; MICROTUBULE; PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION; SRC HOMOLOGY DOMAIN; STRESS FIBER; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELL MEMBRANE; CELL MOVEMENT; CYTOSKELETAL PROTEINS; CYTOSKELETON; FOCAL ADHESION KINASE 1; FOCAL ADHESION PROTEIN-TYROSINE KINASES; HUMANS; INTERCELLULAR JUNCTIONS; PAXILLIN; PHOSPHOPROTEINS; PHOSPHORYLATION; PROTEIN STRUCTURE, TERTIARY; PROTEIN-TYROSINE KINASES; PROTEINS; RETINOBLASTOMA-LIKE PROTEIN P130;

EID: 11244258882     PISSN: 14710072     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrm1549     Document Type: Review

References (126)

1. Brakebusch, C. & Fassler, R. The integrin-actin connection, an eternal love affair. EMBO J. 22, 2324-2333 (2003).
2. DeMali, K. A., Wennerberg, K. & Burridge, K. Integrin signaling to the actin cytoskeleton. Curr. Opin. Cell Biol. 15, 572-582 (2003).
3. Ridley, A. J. et al. Cell migration: integrating signals from front to back. Science 302, 1704-1709 (2003).
4. 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.
5. 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.
6. Webb, D. J. et al. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nature Cell Biol. 6, 154-161 (2004).
7. 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.
8. Ren, X. et al. Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. J. Cell Sci. 113, 3673-3678 (2000).
9. Agochiya, M. et al. Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells. Oncogene 18, 5646-5653 (1999).
10. 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).
11. 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).
12. 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).
13. Ilic, D. et al. Focal adhesion kinase is required for blood vessel morphogenesis. Circ. Res, 92, 300-307 (2003).
14. 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).
15. 1, integrin-containing invadopodia promotes cell invasion. J. Biol. Chem. 277, 12487-12490 (2002).
16. 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).
17. 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.
18. 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.
19. 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).
20. Katsumi, A., Orr, A. W., Tzima, E. & Schwartz, M. A. Integrins in mechanotransduction. J. Biol. Chem. 279, 12001-12004 (2004).
21. 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).
22. 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).
23. Sieg, D. J. et al. FAK integrates growth-factor and integrin signals to promote cell migration. Nature Cell Biol. 2, 249-256 (2000).
24. 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.
25. 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).
26. 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).
27. 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.
28. 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).
29. McKean, D. M. et al. FAK induces expression of Prx1 to promote tenascin-C-dependent fibroblast migration. J. Cell Biol. 161, 393-402 (2003).
30. 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).
31. 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).
32. 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).
33. Schaller, M. D. Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim. Biophys. Acta. 1540, 1-21 (2001).
34. 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.
35. Toutant, M. et al. Alternative splicing controls the mechanisms of FAK autophosphorylation. Mol. Cell. Biol. 22, 7731-7743 (2002).
36. 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.
37. Avraham, H., Park, S. Y., Schinkmann, K. & Avraham, S. RAFTK/Pyk2-mediated cellular signalling. Cell. Signal 12, 123-133 (2000).
38. Klingbell, 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).
39. 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).
40. 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).
41. 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).
42. Abbi, S. et al. Regulation of focal adhesion kinase by a novel protein inhibitor FIP200. Mol. Biol. Cell 13, 3178-3191 (2002).
43. Medley, Q. G. et al. Signaling between focal adhesion kinase and Trio. J. Biol. Chem. 278, 13265-13270 (2003).
44. 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).
45. 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).
46. 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).
47. 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.
48. Turner, C. E. Paxillin and focal adhesion signalling. Nature Cell Biol. 2, 231-236 (2000).
49. 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).
50. Brabek, J. et al. CAS promotes invasiveness of Src-transformed cells. Oncogene 23, 7406-7415 (2004).
51. Schaller, M. D. Paxillin: a focal adhesion-associated adaptor protein. Oncogene 20, 6459-6472 (2001).
52. 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).
53. 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).
54. 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).
55. 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).
56. 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).
57. 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.
58. Cas. Mol. Biol. Cell 12, 1-12 (2001).
59. 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).
60. 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).
61. 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).
62. 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).
63. 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).
64. 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).
65. 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).
66. 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).
67. 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).
68. 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.
69. 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).
70. Visse, R. & Nagase, H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ. Res. 92, 827-839 (2003).
71. 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).
72. 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).
73. 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).
74. 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).
75. 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).
76. 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).
77. 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).
78. 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).
79. Rico, B. et al. Control of axonal branching and synapse formation by focal adhesion kinase. Nature Neurosci. 7, 1059-1069 (2004).
80. 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).
81. 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).
82. Gundersen, G. G., Gomes, E. R. & Wen, Y. Cortical control of microtubule stability and polarization. Curr. Opin. Cell Biol. 16, 106-112 (2004).
83. del Pozo, M. A. et al. Integrins regulate Rac targeting by internalization of membrane domains. Science 303, 839-842 (2004).
84. 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).
85. Slack-Davis, J. K. et al. PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation. J. Cell Biol. 162, 281-291 (2003).
86. 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).
87. 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).
88. Calderwood, D. A. Integrin activation. J. Cell Sci. 117, 657-666 (2004).
89. 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).
90. Di Paolo, G. et al. Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 γ by the FERM domain of talin. Nature 420, 85-89 (2002).
91. 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).
92. 1-integrin cytoplasmic domain bind to the same region in the talin FERM domain. J. Biol. Chem. 278, 31202-31209 (2003).
93. 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.
94. Wheelock, M. J. & Johnson, K. R. Cadherins as modulators of cellular phenotype. Ann. Rev. Cell Dev. Biol. 19, 207-235 (2003).
95. 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).
96. 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).
97. 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).
98. Miranti, C. K. & Brugge, J. S. Sensing the environment: a historical perspective on integrin signal transduction. Nature Cell Biol. 4, E83-E90 (2002).
99. 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).
100. 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.
101. 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).
102. Cukierman, E., Pankov, R. & Yamada, K. M. Cell interactions with three-dimensional matrices. Curr. Opin. Cell Biol. 14, 633-639 (2002).
103. Ilic, D. et al. FAK promotes organization of fibronectin matrix and fibrillar adhesions. J. Cell Sci. 117, 177-187 (2004).
104. 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.
105. Cukierman, E., Pankov, R., Stevens, D. R. & Yamada, K. M. Taking cell-matrix adhesions to the third dimension. Science 294, 1708-1712 (2001).
106. 1 integrin viability signaling pathway. J. Biol. Chem. 279, 33024-33034 (2004).
107. 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).
108. 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).
109. Bowden, E. T., Coopman, P. J. & Mueller, S. C. Invadopodla: unique methods for measurement of extracellular matrix degradation in vitro. Methods Cell Biol. 63, 613-627 (2001).
110. 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).
111. 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).
112. 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).
113. Calderwood, D. A. & Ginsberg, M. H. Talin forges the links between integrins and actin. Nature Cell Biol. 5, 694-697 (2003).
114. Zheng, C. et al. Differential regulation of Pyk2 and focal adhesion kinase (FAK). J. Biol. Chem. 273, 2384-2389 (1998).
115. 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).
116. - cell migration. EMBO J. 17, 5933-5947 (1998).
117. 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).
118. 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).
119. 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).
120. 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.
121. 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).
122. 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).
123. 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).
124. Cas. Nature Genet. 19, 361-365 (1998).
125. 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).
126. Xu, W., Baribault, H. & Adamson, E. D. Vinculin knockout results in heart and brain defects during embryonic development. Development 125, 327-337 (1998).