Focal adhesion kinase: switching between GAPs and GEFs in the regulation of cell motility

Current Opinion in Cell Biology

Volumn 21, Issue 5, 2009, Pages 676-683

  Tomar, Alok ^a   Schlaepfer, David D ^a  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FOCAL ADHESION KINASE; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN;

CELL MOTILITY; CELL STRUCTURE; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME BINDING; ENZYME METABOLISM; ENZYME STRUCTURE; NONHUMAN; PRIORITY JOURNAL; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; CELL ADHESION; CELL MOVEMENT; FOCAL ADHESION PROTEIN-TYROSINE KINASES; GTPASE-ACTIVATING PROTEINS; GUANINE NUCLEOTIDE EXCHANGE FACTORS; SIGNAL TRANSDUCTION;

EID: 70349332774     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ceb.2009.05.006     Document Type: Review

References (51)

1. Vicente-Manzanares M., Webb D.J., and Horwitz A.R. Cell migration at a glance. J Cell Sci 118 (2005) 4917-4919
2. Fukata M., Nakagawa M., and Kaibuchi K. Roles of Rho-family GTPases in cell polarisation and directional migration. Curr Opin Cell Biol 15 (2003) 590-597
3. Jaffe A.B., and Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21 (2005) 247-269
4. Mitra S.K., Hanson D.A., and Schlaepfer D.D. Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol 6 (2005) 56-68
5. Schlaepfer D.D., and Mitra S.K. Multiple connections link FAK to cell motility and invasion. Curr Opin Genet Dev 14 (2004) 92-101
6. Xia N., Thodeti C.K., Hunt T.P., Xu Q., Ho M., Whitesides G.M., Westervelt R., and Ingber D.E. Directional control of cell motility through focal adhesion positioning and spatial control of Rac activation. FASEB J 22 (2008) 1649-1659
7. Mitra S.K., and Schlaepfer D.D. Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol 18 (2006) 516-523
8. Michael K.E., Dumbauld D.W., Burns K.L., Hanks S.K., and Garcia AJ. FAK modulates cell adhesion strengthening via integrin activation. Mol Biol Cell 20 (2009) 2508-2519. FAK facilitates β1 integrin activation and that this linkage requires FAK Y397 phosphorylation and involves talin. FAK-mediated inside-out signaling to β1 integrin occurs early during cell engagement with ECM and results in increased FA strengthening.
9. Friedland J.C., Lee M.H., and Boettiger D. Mechanically activated integrin switch controls alpha5beta1 function. Science 323 (2009) 642-644
10. Zhang X., Jiang G., Cai Y., Monkley S.J., Critchley D.R., and Sheetz M.P. Talin depletion reveals independence of initial cell spreading from integrin activation and traction. Nat Cell Biol 10 (2008) 1062-1068. Combined talin-1 and talin-2 depletion from cells results in a ECM-integrin-cytoskeleton linkage failure that prevents FA assembly and FAK activation but not cell spreading.
11. Deakin N.O., and Turner C.E. Paxillin comes of age. J Cell Sci 121 (2008) 2435-2444
12. Lietha D., Cai X., Ceccarelli D.F., Li Y., Schaller M.D., and Eck M.J. Structural basis for the autoinhibition of focal adhesion kinase. Cell 129 (2007) 1177-1187. This study reveals crystal structures representing both auto-inhibited and active states of the FAK kinase domain. In an intramolecular interaction, the FAK FERM domain makes contact with the FAK kinase domain blocking access to the FAK active site cleft and to the kinase activation loop.
13. Serrels B., Serrels A., Brunton V.G., Holt M., McLean G.W., Gray C.H., Jones G.E., and Frame M.C. Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex. Nat Cell Biol 9 (2007) 1046-1056. The actin nucleating protein Arp3 binds to the FAK FERM domain and this interaction facilitates Arp2/3 complex recruitment to nascent FAs. The FAK-Arp2/3 interaction is disrupted by FAK activation and Y397 phosphorylation providing evidence that it is the scaffolding role of the FAK FERM domain that connects integrin signals to the Arp2/3 complex and cell protrusion.
14. 2)-containing vesicles activated and induced conformational change in FAK and that this was dependent upon conserved basic residues within the FAK FERM domain.
15. Sawada Y., Tamada M., Dubin-Thaler B.J., Cherniavskaya O., Sakai R., Tanaka S., and Sheetz M.P. Force sensing by mechanical extension of the Src family kinase substrate p130Cas. Cell 127 (2006) 1015-1026
16. Papusheva E., de Queiroz F.M., Dalous J., Han Y., Esposito A., Jares-Erijmanxa E.A., Jovin T.M., and Bunt G. Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility. J Cell Sci 122 (2009) 656-666. A positive FRET-based FAK biosensor was developed that visualizes conformational changes of the FAK FERM domain with FAs during discrete phases of cell spreading. These changes in FAK were dependent upon actomyosin tension but not intrinsic FAK activity.
17. Chen S.Y., and Chen H.C. Direct interaction of focal adhesion kinase (FAK) with Met is required for FAK to promote hepatocyte growth factor-induced cell invasion. Mol Cell Biol 26 (2006) 5155-5167
18. Wu L., Bernard-Trifilo J.A., Lim Y., Lim S.T., Mitra S.K., Uryu S., Chen M., Pallen C.J., Cheung N.K., Mikolon D., et al. Distinct FAK-Src activation events promote alpha5beta1 and alpha4beta1 integrin-stimulated neuroblastoma cell motility. Oncogene 27 (2008) 1439-1448. FAK activity is required for α5β1-stimulated cell motility and Src activation via direct FAK phosphorylation of Src Y416 within the kinase activation loop.
19. Carlucci A., Gedressi C., Lignitto L., Nezi L., Villa-Moruzzi E., Avvedimento E.V., Gottesman M., Garbi C., and Feliciello A. Protein-tyrosine phosphatase PTPD1 regulates focal adhesion kinase autophosphorylation and cell migration. J Biol Chem 283 (2008) 10919-10929
20. Defilippi P., Di Stefano P., and Cabodi S. p130Cas: a versatile scaffold in signaling networks. Trends Cell Biol 16 (2006) 257-263
21. Ricono J.M., Huang M., Barnes L.A., Lau S.K., Weis S.M., Schlaepfer D.D., Hanks S.K., and Cheresh D.A. Specific cross-talk between epidermal growth factor receptor and integrin alphavbeta5 promotes carcinoma cell invasion and metastasis. Cancer Res 69 (2009) 1383-1391
22. Chan K.T., Cortesio C.L., and Huttenlocher A. FAK alters invadopodia and focal adhesion composition and dynamics to regulate breast cancer invasion. J Cell Biol 185 (2009) 357-370
23. •], this study describes the loss of FAK from cells results in elevated Rac GTPase activation and multiple leading edge forming structures. FAK expression and Y397 phosphorylation are shown to be important for leading edge formation in migrating cells. FAK acts to connect integrin signals to direct the correct spatial activation of membrane protrusion.
24. •]
25. Pertz O., Hodgson L., Klemke R.L., and Hahn K.M. Spatiotemporal dynamics of RhoA activity in migrating cells. Nature 440 (2006) 1069-1072
26. Kurokawa K., Nakamura T., Aoki K., and Matsuda M. Mechanism and role of localized activation of Rho-family GTPases in growth factor-stimulated fibroblasts and neuronal cells. Biochem Soc Trans 33 (2005) 631-634
27. Wildenberg G.A., Dohn M.R., Carnahan R.H., Davis M.A., Lobdell N.A., and Settleman J. Reynolds AB, p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho. Cell 127 (2006) 1027-1039
28. Tomar A., Lim S.-T., Lim Y., and Schlaepfer DD. A FAK, p120RasGAP, and p190RhoGAP complex regulates polarity in migrating cells. J Cell Sci 122 (2009) 1852-1862. Fibroblast, endothelial, and carcinoma cell polarity is associated with the formation of a complex between FAK, p120RasGAP, and p190RhoGAP leading to p190RhoGAP tyrosine phosphorylation. FAK activation serves as a key event to facilitate the recruitment and stabilization of a p120RasGAP-p190RhoGAP complex at leading edge focal adhesions connected to the regulation of cell polarity.
29. Lim Y., Lim S.T., Tomar A., Gardel M., Bernard-Trifilo J.A., Chen X.L., Uryu S.A., Canete-Soler R., Zhai J., Lin H., et al. PyK2 and FAK connections to p190Rho guanine nucleotide exchange factor regulate RhoA activity, focal adhesion formation, and cell motility. J Cell Biol 180 (2008) 187-203. p190RhoGEF (Rgnef) was identified as an important facilitator of RhoA GTPase activation and FA formation upon fibroblast spreading on fibronectin. FA localization and Rgnef tyrosine phosphorylation were dependent upon FAK binding. This study provides molecular insights into how both FAK activity and scaffolding contribute to the regulating of RhoGTPases.
30. Arthur W.T., and Burridge K. RhoA inactivation by p190RhoGAP regulates cell spreading and migration by promoting membrane protrusion and polarity. Mol Biol Cell 12 (2001) 2711-2720
31. Ren X., Kiosses W.B., Sieg D.J., Otey C.A., Schlaepfer D.D., and Schwartz M.A. Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. J Cell Sci 113 (2000) 3673-3678
32. Chikumi H., Fukuhara S., and Gutkind J.S. Regulation of G protein-linked guanine nucleotide exchange factors for Rho, PDZ-RhoGEF, and LARG by tyrosine phosphorylation: evidence of a role for focal adhesion kinase. J Biol Chem 277 (2002) 12463-12473
33. Hata K., Kaibuchi K., Inagaki S., and Yamashita T. Unc5B associates with LARG to mediate the action of repulsive guidance molecule. J Cell Biol 184 (2009) 737-750
34. Iwanicki M.P., Vomastek T., Tilghman R.W., Martin K.H., Banerjee J., Wedegaertner P.B., and Parsons J.T. FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts. J Cell Sci 121 (2008) 895-905. A FAK and PDZ-RhoGEF complex was implicated in promoting trailing edge cell retraction in migrating cells via Rho/ROCKII-dependent FA movement.
35. Dubash A.D., Wennerberg K., Garcia-Mata R., Menold M.M., Arthur W.T., and Burridge K. A novel role for Lsc/p115 RhoGEF and LARG in regulating RhoA activity downstream of adhesion to fibronectin. J Cell Sci 120 (2007) 3989-3998
36. Zhu Y., Wu Y., Kim J.I., Wang Z., Daaka Y., and Nie Z. The Arf GTPase-activating protein AGAP2 regulates focal adhesion kinase activity and focal adhesion remodeling. J Biol Chem 284 (2009) 13489-13496
37. Webb D.J., Donais K., Whitmore L.A., Thomas S.M., Turner C.E., Parsons J.T., and Horwitz A.F. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol 6 (2004) 154-161
38. Zaidel-Bar R., Ballestrem C., Kam Z., and Geiger B. Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells. J Cell Sci 116 (2003) 4605-4613
39. Broussard J.A., Webb D.J., and Kaverina I. Asymmetric focal adhesion disassembly in motile cells. Curr Opin Cell Biol 20 (2008) 85-90
40. Ilic D., Furuta Y., Kanazawa S., Takeda N., Sobue K., Nakatsuji N., Nomura S., Fujimoto J., Okada M., Yamamoto T., et al. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377 (1995) 539-544
41. Hsia D.A., Mitra S.K., Hauck C.R., Streblow D.N., Nelson J.A., Ilic D., Huang S., Li E., Nemerow G.R., Leng J., et al. Differential regulation of cell motility and invasion by FAK. J Cell Biol 160 (2003) 753-767
42. Lim S.T., Chen X.L., Lim Y., Hanson D.A., Vo T.T., Howerton K., Larocque N., Fisher S.J., Schlaepfer D.D., and Ilic D. Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation. Mol Cell 29 (2008) 9-22
43. Giannone G., Ronde P., Gaire M., Beaudouin J., Haiech J., Ellenberg J., and Takeda K. Calcium rises locally trigger focal adhesion disassembly and enhance residency of focal adhesion kinase at focal adhesions. J Biol Chem 279 (2004) 28715-28723
44. Joshi B., Strugnell S.S., Goetz J.G., Kojic L.D., Cox M.E., Griffith O.L., Chan S.K., Jones S.J., Leung S.P., Masoudi H., et al. Phosphorylated caveolin-1 regulates Rho/ROCK-dependent focal adhesion dynamics and tumor cell migration and invasion. Cancer Res 68 (2008) 8210-8220
45. Zaidel-Bar R., Milo R., Kam Z., and Geiger B. A paxillin tyrosine phosphorylation switch regulates the assembly and form of cell-matrix adhesions. J Cell Sci 120 (2007) 137-148. FAK-mediated phosphorylation of paxillin at Y31 and Y118 increased FAK-paxillin binding which was correlated with increased turnover of FAs. The authors propose a model whereby adhesion dynamics are controlled via FAK recruitment and paxillin phosphorylation.
46. Hamadi A., Bouali M., Dontenwill M., Stoeckel H., Takeda K., and Ronde P. Regulation of focal adhesion dynamics and disassembly by phosphorylation of FAK at tyrosine 397. J Cell Sci 118 (2005) 4415-4425
47. Gupton S.L., and Waterman-Storer C.M. Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration. Cell 125 (2006) 1361-1374
48. Schober M., Raghavan S., Nikolova M., Polak L., Pasolli H.A., Beggs H.E., Reichardt L.F., and Fuchs E. Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics. J Cell Biol 176 (2007) 667-680. In FAK-null keratinocytes, cytoskeletal and FA structures are altered and cells exhibit defects in cell motility. Src and p190RhoGAP localization and/or activation at FAs are impaired and these stuydies establish a connection between FAK, p190RhoGAP tyrosine phosphorylation, and the regulation of RhoGTPase activity.
49. Chang F., Lemmon C.A., Park D., and Romer L.H. FAK potentiates Rac1 activation and localization to matrix adhesion sites: a role for betaPIX. Mol Biol Cell 18 (2007) 253-264
50. Franco S.J., and Huttenlocher A. Regulating cell migration: calpains make the cut. J Cell Sci 118 (2005) 3829-3838
51. Barbero S., Mielgo A., Torres V., Teitz T., Shields D.J., Mikolon D., Bogyo M., Barila D., Lahti J.M., Schlaepfer D., et al. Caspase-8 association with the focal adhesion complex promotes tumor cell migration and metastasis. Can Res 69 (2009) 3755-3763