Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Focal Adhesion Kinase (FAK)

  • Haiqi Chen
  • C. Yan ChengEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101628


Historical Background

Focal adhesion kinase (FAK), a non-receptor protein-tyrosine kinase found in virtually all mammalian cells (Mitra et al. 2005; Frame et al. 2011) and crucial to integrin-based signaling (Alanko and Ivaska 2016). FAK was originally identified in 1990 as an ~125 kDa (p125/pp125) phosphoprotein (Kanner et al. 1990). FAK was later shown to be a cytosolic protein mostly accumulated at focal adhesions at the cell-matrix interface, and it was designated pp125FAK (Schaller et al. 1992). An increase in tyrosine phosphorylation of pp125FAK was detected during cell adhesion to fibronectin (Hanks et al. 1992). Furthermore, cells treated with a specific protein-tyrosine kinase inhibitor herbimycin A led to a decrease in focal adhesion and stress fiber formation (Burridge et al. 1992). These earlier observations thus illustrate that tyrosine phosphorylation of FAK plays a role in cytoskeletal...

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This work was supported by grants from the National Institutes of Health, NICHD, R01 HD056034 to C.Y. C., and U54 HD029990 Project 5 to C.Y.C.


  1. Alanko J, Ivaska J. Endosomes: emerging platforms for integrin-mediated FAK signalling. Trends Cell Biol. 2016;26:391–8.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Ashton GH, Morton JP, Myant K, Phesse TJ, Ridgway RA, Marsh V, et al. Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling. Dev Cell. 2010;19:259–69.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Beardsley A, Robertson DM, O’Donnell L. A complex containing alpha6beta1-integrin and phosphorylated focal adhesion kinase between Sertoli cells and elongated spermatids during spermatid release from the seminiferous epithelium. J Endocrinol. 2006;190:759–70.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Brown MC, Perrotta JA, Turner CE. Identification of LIM3 as the principal determinant of paxillin focal adhesion localization and characterization of a novel motif on paxillin directing vinculin and focal adhesion kinase binding. J Cell Biol. 1996;135:1109–23.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Brunton VG, Frame MC. Src and focal adhesion kinase as therapeutic targets in cancer. Curr Opin Pharmacol. 2008;8:427–32.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Burridge K, Turner CE, Romer LH. Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly. J Cell Biol. 1992;119:893–903.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Byron A, Frame MC. Adhesion protein networks reveal functions proximal and distal to cell-matrix contacts. Curr Opin Cell Biol. 2016;39:93–100.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Cai X, Lietha D, Ceccarelli DF, Karginov AV, Rajfur Z, Jacobson K, et al. Spatial and temporal regulation of focal adhesion kinase activity in living cells. Mol Cell Biol. 2008;28:201–14.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Calalb MB, Polte TR, Hanks SK. Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src family kinases. Mol Cell Biol. 1995;15:954–63.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Calalb MB, Zhang X, Polte TR, Hanks SK. Focal adhesion kinase tyrosine-861 is a major site of phosphorylation by Src. Biochem Biophys Res Commun. 1996;228:662–8.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Cary LA, Chang JF, Guan JL. Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn. J Cell Sci. 1996;109(Pt 7):1787–94.PubMedPubMedCentralGoogle Scholar
  12. Chen HC, Appeddu PA, Isoda H, Guan JL. Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase. J Biol Chem. 1996;271:26329–34.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Chen HC, Appeddu PA, Parsons JT, Hildebrand JD, Schaller MD, Guan JL. Interaction of focal adhesion kinase with cytoskeletal protein talin. J Biol Chem. 1995;270:16995–9.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Chen HC, Guan JL. Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase. Proc Natl Acad Sci U S A. 1994;91:10148–52.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Chen R, Kim O, Li M, Xiong X, Guan JL, Kung HJ, et al. Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain. Nat Cell Biol. 2001;3:439–44.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Chen SY, Chen HC. Direct interaction of focal adhesion kinase (FAK) with Met is required for FAK to promote hepatocyte growth factor-induced cell invasion. Mol Cell Biol. 2006;26:5155–67.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Cheng CY, Mruk DD. The blood-testis barrier and its implication in male contraception. Pharmacol Rev. 2012;64:16–64.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Cheng CY, Mruk DD. Cell junction dynamics in the testis: Sertoli-germ cell interactions and male contraceptive development. Physiol Rev. 2002;82:825–74.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Cheng CY, Mruk DD. Regulation of blood-testis barrier dynamics by focal adhesion kinase (FAK). An unexpected turn of events. Cell Cycle. 2009;8:3493–9.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Cheng CY, Mruk DD. Regulation of spermiogenesis, spermiation and blood-testis barrier dynamics: novel insights from studies on Eps8 and Arp3. Biochem J. 2011;435:553–62.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Chishti AH, Kim AC, Marfatia SM, Lutchman M, Hanspal M, Jindal H, et al. The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends Biochem Sci. 1998;23:281–2.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Cobb BS, Schaller MD, Leu TH, Parsons JT. Stable association of pp60src and pp59fyn with the focal adhesion-associated protein tyrosine kinase, pp125FAK. Mol Cell Biol. 1994;14:147–55.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Cooper LA, Shen TL, Guan JL. Regulation of focal adhesion kinase by its amino-terminal domain through an autoinhibitory interaction. Mol Cell Biol. 2003;23:8030–41.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Dunty JM, Schaller MD. The N termini of focal adhesion kinase family members regulate substrate phosphorylation, localization, and cell morphology. J Biol Chem. 2002;277:45644–54.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Dym M. Basement membrane regulation of Sertoli cells. Endocr Rev. 1994;15:102–15.PubMedPubMedCentralGoogle Scholar
  26. Fang XQ, Liu XF, Yao L, Chen CQ, ZD G, Ni PH, et al. Somatic mutational analysis of FAK in breast cancer: a novel gain-of-function mutation due to deletion of exon 33. Biochem Biophys Res Commun. 2014;443:363–9.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Figel S, Gelman IH. Focal adhesion kinase controls prostate cancer progression via intrinsic kinase and scaffolding functions. Anticancer Agents Med Chem. 2011;11:607–16.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Fox GL, Rebay I, Hynes RO. Expression of DFak56, a Drosophila homolog of vertebrate focal adhesion kinase, supports a role in cell migration in vivo. Proc Natl Acad Sci U S A. 1999;96:14978–83.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Frame MC, Patel H, Serrels B, Lietha D, Eck MJ. The FERM domain: organizing the structure and function of FAK. Nat Rev Mol Cell Biol. 2011;11:802–14.CrossRefGoogle Scholar
  30. Frame MC, Patel H, Serrels B, Lietha D, Eck MJ. The FERM domain: organizing the structure and function of FAK. Nat Rev Mol Cell Biol. 2010;11:802–14.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Frisch SM, Vuori K, Ruoslahti E, Chan-Hui PY. Control of adhesion-dependent cell survival by focal adhesion kinase. J Cell Biol. 1996;134:793–9.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Grigera PR, Jeffery ED, Martin KH, Shabanowitz J, Hunt DF, Parsons JTFAK. phosphorylation sites mapped by mass spectrometry. J Cell Sci. 2005;118:4931–5.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Han DC, Guan JL. Association of focal adhesion kinase with Grb7 and its role in cell migration. J Biol Chem. 1999;274:24425–30.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Hanks SK, Calalb MB, Harper MC, Patel SK. Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc Natl Acad Sci U S A. 1992;89:8487–91.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Henry CA, Crawford BD, Yan YL, Postlethwait J, Cooper MS, Hille MB. Roles for zebrafish focal adhesion kinase in notochord and somite morphogenesis. Dev Biol. 2001;240:474–87.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Hildebrand JD, Schaller MD, Parsons JT. Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions. J Cell Biol. 1993;123:993–1005.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Hunger-Glaser I, Fan RS, 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. 2004;200:213–22.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Ilic D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, et al. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature. 1995;377:539–44.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Infante JR, Camidge DR, Mileshkin LR, Chen EX, Hicks RJ, Rischin D, et al. Safety, pharmacokinetic, and pharmacodynamic phase I dose-escalation trial of PF-00562271, an inhibitor of focal adhesion kinase, in advanced solid tumors. J Clin Oncol. 2012;30:1527–33.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Iwakuma T, Lozano G. MDM2, an introduction. Mol Cancer Res. 2003;1:993–1000.PubMedPubMedCentralGoogle Scholar
  41. Jacamo R, Jiang X, Lunn JA, Rozengurt E. FAK phosphorylation at Ser-843 inhibits Tyr-397 phosphorylation, cell spreading and migration. J Cell Physiol. 2007;210:436–44.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Jayachandran A, Dhungel B, Steel JC. Epithelial-to-mesenchymal plasticity of cancer stem cells: therapeutic targets in hepatocellular carcinoma. J Hematol Oncol. 2016;9:74.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Jung Y, McCarty JH. Band 4.1 proteins regulate integrin-dependent cell spreading. Biochem Biophys Res Commun. 2012;426:578–84.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Kanner SB, Reynolds AB, Vines RR, Parsons JT. Monoclonal antibodies to individual tyrosine-phosphorylated protein substrates of oncogene-encoded tyrosine kinases. Proc Natl Acad Sci U S A. 1990;87:3328–32.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Kanteti R, Batra SK, Lennon FE, Salgia R. FAK and paxillin, two potential targets in pancreatic cancer. Oncotarget. 2016.Google Scholar
  46. Klein EA, Yin L, Kothapalli D, Castagnino P, Byfield FJ, Xu T, et al. Cell-cycle control by physiological matrix elasticity and in vivo tissue stiffening. Curr Biol. 2009;19:1511–8.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Kratimenos P, Koutroulis I, Marconi D, Syriopoulou V, Delivoria-Papadopoulos M, Chrousos GP, et al. Multi-targeted molecular therapeutic approach in aggressive neuroblastoma: the effect of Focal Adhesion Kinase–Src–Paxillin system. Expert Opin Ther Targets. 2014;18:1395–406.PubMedPubMedCentralGoogle Scholar
  48. Lauffenburger DA, Horwitz AF. Cell migration: a physically integrated molecular process. Cell. 1996;84:359–69.CrossRefPubMedGoogle Scholar
  49. Leavitt T, MS H, Marshall CD, Barnes LA, Lorenz HP, Longaker MT. Scarless wound healing: finding the right cells and signals. Cell Tissue Res. 2016;365:483–93.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Li SY, Mruk DD, Cheng CY. Focal adhesion kinase is a regulator of F-actin dynamics: New insights from studies in the testis. Spermatogenesis. 2013;3:e25385.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Lie PPY, Mruk DD, Lee WM, Cheng CY. Epidermal growth factor receptor pathway substrate 8 (Eps8) is a novel regulator of cell adhesion and the blood-testis barrier integrity in the seminiferous epithelium. FASEB J. 2009;23:2555–67.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Lie PPY, Mruk DD, Mok KW, Su L, Lee WM, Cheng CY. Focal adhesion kinase-Tyr407 and -Tyr397 exhibit antagonistic effects on blood-testis barrier dynamics in the rat. Proc Natl Acad Sci U S A. 2012;109:12562–7.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Lim ST, Chen XL, Lim Y, Hanson DA, Vo TT, Howerton K, et al. Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation. Mol Cell. 2008;29:9–22.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Lim ST, Miller NL, Chen XL, Tancioni I, Walsh CT, Lawson C, et al. Nuclear-localized focal adhesion kinase regulates inflammatory VCAM-1 expression. J Cell Biol. 2012;197:907–19.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Ling K, Doughman RL, Iyer VV, Firestone AJ, Bairstow SF, Mosher DF, et al. Tyrosine phosphorylation of type Igamma phosphatidylinositol phosphate kinase by Src regulates an integrin-talin switch. J Cell Biol. 2003;163:1339–49.PubMedPubMedCentralCrossRefGoogle Scholar
  56. Luo M, Fan H, Nagy T, Wei H, Wang C, Liu S, et al. Mammary epithelial-specific ablation of the focal adhesion kinase suppresses mammary tumorigenesis by affecting mammary cancer stem/progenitor cells. Cancer Res. 2009;69:466–74.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Ma A, Richardson A, Schaefer EM, Parsons JT. Serine phosphorylation of focal adhesion kinase in interphase and mitosis: a possible role in modulating binding to p130(Cas). Mol Biol Cell. 2001;12:1–12.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Machesky LM. Lamellipodia and filopodia in metastasis and invasion. FEBS Lett. 2008;582:2102–11.PubMedPubMedCentralCrossRefGoogle Scholar
  59. McLean GW, Komiyama NH, Serrels B, Asano H, Reynolds L, Conti F, et al. Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression. Genes Dev. 2004;18:2998–3003.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Mitra SK, Hanson DA, Schlaepfer DD. Focal adhesion kinase: in command and control of cell motility. Nature Rev Mol Cell Biol. 2005;6:56–68.PubMedPubMedCentralCrossRefGoogle Scholar
  61. Mruk DD, Cheng CY. Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis. Endocr Rev. 2004;25:747–806.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Mui KL, Bae YH, Gao L, Liu SL, Xu T, Radice GL, et al. N-Cadherin Induction by ECM Stiffness and FAK Overrides the Spreading Requirement for Proliferation of Vascular Smooth Muscle Cells. Cell Rep. 2015.Google Scholar
  63. O’Donnell L, Nicholls PK, O’Bryan MK, McLachlan RI, Stanton PG. Spermiation: the process of sperm release. Spermatogenesis. 2011;1:14–35.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Ossovskaya V, Lim ST, Ota N, Schlaepfer DD, Ilic DFAK. nuclear export signal sequences. FEBS Lett. 2008;582:2402–6.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Owens LV, Xu L, Craven RJ, Dent GA, Weiner TM, Kornberg L, et al. Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. Cancer Res. 1995;55:2752–5.PubMedPubMedCentralGoogle Scholar
  66. Owens LV, Xu L, Dent GA, Yang X, Sturge GC, Craven RJ, et al. Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer. Ann Surg Oncol. 1996;3:100–5.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Owens LV, Xu L, Marston WA, Yang X, Farber MA, Iacocca MV, et al. Overexpression of the focal adhesion kinase (p125FAK) in the vascular smooth muscle cells of intimal hyperplasia. J Vasc Surg. 2001;34:344–9.PubMedPubMedCentralCrossRefGoogle Scholar
  68. Park AY, Shen TL, Chien S, Guan JL. Role of focal adhesion kinase Ser-732 phosphorylation in centrosome function during mitosis. J Biol Chem. 2009;284:9418–25.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Park JH, Lee BL, Yoon J, Kim J, Kim MA, Yang HK, et al. Focal adhesion kinase (FAK) gene amplification and its clinical implications in gastric cancer. Hum Pathol. 2010;41:1664–73.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Parsons JT. Focal adhesion kinase: the first ten years. J Cell Sci. 2003;116:1409–16.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Polte TR, Hanks SK. Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas. Proc Natl Acad Sci U S A. 1995;92:10678–82.PubMedPubMedCentralCrossRefGoogle Scholar
  72. Poullet P, Gautreau A, Kadare G, Girault JA, Louvard D, Arpin M. Ezrin interacts with focal adhesion kinase and induces its activation independently of cell-matrix adhesion. J Biol Chem. 2001;276:37686–91.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Pylayeva Y, Gillen KM, Gerald W, Beggs HE, Reichardt LF, Giancotti FG. Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling. J Clin Invest. 2009;119:252–66.PubMedPubMedCentralGoogle Scholar
  74. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.PubMedPubMedCentralCrossRefGoogle Scholar
  75. Romer LH, McLean N, Turner CE, Burridge K. Tyrosine kinase activity, cytoskeletal organization, and motility in human vascular endothelial cells. Mol Biol Cell. 1994;5:349–61.PubMedPubMedCentralCrossRefGoogle Scholar
  76. Russell L, Clermont Y. Anchoring device between Sertoli cells and late spermatids in rat seminiferous tubules. Anat Rec. 1976;185:259–78.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Schaller MD, Borgman CA, Cobb BS, Vines RR, Reynolds AB, Parsons JT. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A. 1992;89:5192–6.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Schaller MD, Hildebrand JD, Shannon JD, Fox JW, Vines RR, Parsons JT. Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src. Mol Cell Biol. 1994;14:1680–8.PubMedPubMedCentralCrossRefGoogle Scholar
  79. Schaller MD, Otey CA, Hildebrand JD, Parsons JT. Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains. J Cell Biol. 1995;130:1181–7.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Schlaepfer DD, Hanks SK, Hunter T, van der Geer P. Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. Nature. 1994;372:786–91.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Schlaepfer DD, Hauck CR, Sieg DJ. Signaling through focal adhesion kinase. Prog Biophys Mol Biol. 1999;71:435–78.PubMedPubMedCentralCrossRefGoogle Scholar
  82. Schober M, Fuchs E. Tumor-initiating stem cells of squamous cell carcinomas and their control by TGF-beta and integrin/focal adhesion kinase (FAK) signaling. Proc Natl Acad Sci U S A. 2011;108:10544–9.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Serrels B, Sandilands E, Serrels A, Baillie G, Houslay MD, Brunton VG, et al. A complex between FAK, RACK1, and PDE4D5 controls spreading initiation and cancer cell polarity. Curr Biol. 2010;20:1086–92.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Serrels B, Serrels A, Brunton VG, Holt M, McLean GW, Gray CH, et al. Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex. Nat Cell Biology. 2007;9:1046–1056.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Setchell BP. Blood-testis barrier, functional and transport proteins and spermatogenesis. Adv Exp Med Biol. 2008;636:212–33.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Shen TL, Park AY, Alcaraz A, Peng X, Jang I, Koni P, et al. Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. J Cell Biol. 2005;169:941–52.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Shi Q, Hjelmeland AB, Keir ST, Song L, Wickman S, Jackson D, et al. A novel low-molecular weight inhibitor of focal adhesion kinase, TAE226, inhibits glioma growth. Mol Carcinog. 2007;46:488–96.PubMedPubMedCentralCrossRefGoogle Scholar
  88. Sieg DJ, Hauck CR, Schlaepfer DD. Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration. J Cell Sci. 1999;112(Pt 16):2677–91.PubMedPubMedCentralGoogle Scholar
  89. Siu ER, Wong EWP, Mruk DD, Porto CS, Cheng CY. Focal adhesion kinase is a blood-testis barrier regulator. Proc Natl Acad Sci U S A. 2009;106:9298–303.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Siu MK, Mruk DD, Lee WM, Cheng CY. Adhering junction dynamics in the testis are regulated by an interplay of beta 1-integrin and focal adhesion complex-associated proteins. Endocrinology. 2003;144:2141–63.PubMedPubMedCentralCrossRefGoogle Scholar
  91. Siu MKY, Cheng CY. Dynamic cross-talk between cells and the extracellular matrix in the testis. BioEssays. 2004;26:978–92.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Siu MKY, Wong CH, Lee WM, Cheng CY. Sertoli-germ cell anchoring junction dynamics in the testis are regulated by an interplay of lipid and protein kinases. J Biol Chem. 2005;280:25029–47.PubMedPubMedCentralCrossRefGoogle Scholar
  93. Siu MKY, Wong CH, Xia W, Mruk DD, Lee WM, Cheng CY. The β1-integrin-p-FAK-p130Cas-DOCK180-RhoA-vinculin is a novel regulatory protein complex at the apical ectoplasmic specialization in adult rat testes. Spermatogenesis. 2011;1:73–86.PubMedPubMedCentralCrossRefGoogle Scholar
  94. Slack-Davis JK, Martin KH, Tilghman RW, Iwanicki M, Ung EJ, Autry C, et al. Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 2007;282:14845–52.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Slack JK, Adams RB, Rovin JD, Bissonette EA, Stoker CE, Parsons JT. Alterations in the focal adhesion kinase/Src signal transduction pathway correlate with increased migratory capacity of prostate carcinoma cells. Oncogene. 2001;20:1152–63.PubMedPubMedCentralCrossRefGoogle Scholar
  96. Taylor JM, Hildebrand JD, Mack CP, Cox ME, Parsons JT. Characterization of graf, the GTPase-activating protein for rho associated with focal adhesion kinase. Phosphorylation and possible regulation by mitogen-activated protein kinase. J Biol Chem. 1998;273:8063–70.PubMedPubMedCentralCrossRefGoogle Scholar
  97. van Miltenburg MH, van Nimwegen MJ, Tijdens I, Lalai R, Kuiper R, Klarenbeek S, et al. Mammary gland-specific ablation of focal adhesion kinase reduces the incidence of p53-mediated mammary tumour formation. Br J Cancer. 2014;110:2747–55.PubMedPubMedCentralCrossRefGoogle Scholar
  98. Wan HT, Mruk DD, Li SYT, Mok KW, Lee WM, Wong CKC, et al. p-FAK-Tyr397 regulates spermatid adhesion in the rat testis via its effects on F-actin organization at the ectoplasmic specialization. Am J Physiol Endocrinol Metab. 2013;305:E687–E99.PubMedPubMedCentralCrossRefGoogle Scholar
  99. Wan HT, Mruk DD, Wong CK, Cheng CY. Perfluorooctanesulfonate (PFOS) perturbs male rat Sertoli cell blood-testis barrier function by affecting F-actin organization via p-FAK-Tyr(407): an in vitro study. Endocrinology. 2014;155:249–62.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Wu X, Suetsugu S, Cooper LA, Takenawa T, Guan JL. Focal adhesion kinase regulation of N-WASP subcellular localization and function. J Biol Chem. 2004;279:9565–76.PubMedPubMedCentralCrossRefGoogle Scholar
  101. Xiao X, Mruk DD, Wong CK, Cheng CY. Germ cell transport across the seminiferous epithelium during spermatogenesis. Physiology (Bethesda). 2014;29:286–98.Google Scholar
  102. Xie Z, Sanada K, Samuels BA, Shih H, Tsai LH. Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration. Cell. 2003;114:469–82.PubMedPubMedCentralCrossRefGoogle Scholar
  103. Xing Z, Chen HC, Nowlen JK, Taylor SJ, Shalloway D, Guan JL. Direct interaction of v-Src with the focal adhesion kinase mediated by the Src SH2 domain. Mol Biol Cell. 1994;5:413–21.PubMedPubMedCentralCrossRefGoogle Scholar
  104. Xu LH, Yang X, Bradham CA, Brenner DA, Baldwin Jr AS, Craven RJ, et al. The focal adhesion kinase suppresses transformation-associated, anchorage-independent apoptosis in human breast cancer cells. Involvement of death receptor-related signaling pathways. J Biol Chem. 2000;275:30597–604.PubMedPubMedCentralCrossRefGoogle Scholar
  105. Yom CK, Noh DY, Kim WH, Kim HS. Clinical significance of high focal adhesion kinase gene copy number and overexpression in invasive breast cancer. Breast Cancer Res Treat. 2011;128:647–55.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Yoon H, Dehart JP, Murphy JM, Lim ST. Understanding the roles of FAK in cancer: inhibitors, genetic models, and new insights. J Histochem Cytochem. 2014;63:114–28.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Zhao JH, Reiske H, Guan JL. Regulation of the cell cycle by focal adhesion kinase. J Cell Biol. 1998;143:1997–2008.PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population CouncilNew YorkUSA