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Gene Review

Ptk2  -  PTK2 protein tyrosine kinase 2

Mus musculus

Synonyms: FADK 1, FAK, FRNK, Fadk, Fak, ...
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Disease relevance of Ptk2


High impact information on Ptk2


Chemical compound and disease context of Ptk2

  • The inhibition of RhoA by the C3 toxin (Clostridium botulinum toxin) restored endothelial barrier function in the FRNK-expressing cells [7].
  • Additionally, treatment of cells with Clostridium difficile toxin B potently inhibited hyperosmotic stress-induced FAK tyrosine phosphorylation [8].
  • Re-expression of the tumor suppressor NF2/merlin inhibits invasiveness in mesothelioma cells and negatively regulates FAK [9].
  • We tested the hypothesis that FAK is a determinant of gemcitabine chemoresistance in pancreatic adenocarcinoma cells and examined the effect of inhibiting FAK expression on gemcitabine-induced cytotoxicity in vitro and in vivo [10].
  • These results demonstrate that combination treatment with EGCG and dacarbazine strongly inhibits melanoma growth and metastasis, and the action mechanisms of EGCG are associated with the inhibition of cell spreading, cell-extracellular matrix and cell-cell interactions, MMP-9 and FAK activities [11].

Biological context of Ptk2


Anatomical context of Ptk2

  • Here we show that cell-specific ablation of the murine gene Ptk2 (more commonly known as fak), encoding focal adhesion kinase (FAK), increases the number of axonal terminals and synapses formed by neurons in vivo [15].
  • Our results show that fibronectin binding to integrins on NIH3T3 fibroblasts promotes c-Src and FAK association and formation of an integrin-activated signalling complex [12].
  • FAK activity can influence the formation of distinct actin cytoskeletal structures such as lamellipodia and stress fibers in part through effects on small Rho GTPases, although the molecular interconnections of these events are not well defined [16].
  • The FAK-deficient mast cells had a reduction in the content of chondroitin/dermatan sulfate, the major glycosaminoglycan component of the granular matrix [17].
  • The FAK-deficient cells had fewer microvilli that were fused with each other, giving the cell surface a ruffled appearance [17].

Associations of Ptk2 with chemical compounds


Physical interactions of Ptk2

  • In all cases, phosphorylation of the putative Grb2-binding site in Fak (Tyr-925) was almost undetectable [20].
  • It resulted from decreased activity of Src family tyrosine kinase and/or decreased amount of Src kinase interacting with pp125FAK [19].
  • This correlated with increased coprecipitation of SSeCKS with biotin-phalloidin-bound F-actin from FAK-/- compared to FAK+/+ cell lysates [21].
  • Also, TNF-induced association of FAK with RIP and subsequent association of RIP with TRAF2 were not observed, resulting in a failure of RIP to recruit the IKK complex in FAK-/- cells [22].
  • First, a beta1 integrin subunit deletion mutant affecting the putative FAK binding site supports activation of MAP kinase in adhering fibroblasts but not tyrosine phosphorylation of FAK [23].

Enzymatic interactions of Ptk2

  • Src and FAK kinases cooperate to phosphorylate paxillin kinase linker, stimulate its focal adhesion localization, and regulate cell spreading and protrusiveness [24].
  • It was found that FCS and fibronectin stimulated phosphorylating activity of FAK in the cells at the logarithmic phase of growth, but were inefficient in the confluent cells [25].
  • Recently, we found that Cdk5 phosphorylates focal adhesion kinase (FAK) at Serine 732 in vitro and is responsible for this phosphorylation in the developing brain [26].
  • Our data show that Src kinase activity is required for adhesion turnover associated with cell migration in cancer cells and that, in addition to the catalytic activity, Src also acts as an adaptor to recruit other kinases that can phosphorylate key substrates including FAK [27].
  • Overexpression of N17 Rac only slightly altered the hyperosmotic stress-mediated localization of phosphorylated FAK to focal contacts [8].

Regulatory relationships of Ptk2


Other interactions of Ptk2

  • This increase is shown to result from vinculin's modulation of paxillin-FAK interactions [32].
  • In this study, we show that over-expression of PYK2, but not FAK, in rat and mouse fibroblasts leads to apoptotic cell death [14].
  • Primary murine embryonic fibroblasts (MEFs) derived from mutant homozygotes display defective cell cycle coupled to impaired activation of the FAK-PI3K-Akt and Rac-JNK signaling pathways [33].
  • Tyr-576 and Tyr-577 lie in the putative activation loop of the kinase domain, and FAK catalytic activity may be elevated through phosphorylation of these residues by associated Src family kinase [28].
  • These defects were associated with deficiencies of PAK1, GSK3beta, myosin light chain, and FAK phosphorylation [34].

Analytical, diagnostic and therapeutic context of Ptk2


  1. FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth. Hauck, C.R., Hsia, D.A., Puente, X.S., Cheresh, D.A., Schlaepfer, D.D. EMBO J. (2002) [Pubmed]
  2. Focal adhesion kinase plays a pivotal role in herpes simplex virus entry. Cheshenko, N., Liu, W., Satlin, L.M., Herold, B.C. J. Biol. Chem. (2005) [Pubmed]
  3. Sustained activation of MAPK/ERKs signaling pathway in cystic kidneys from bcl-2 -/- mice. Sorenson, C.M., Sheibani, N. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  4. Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration. Xie, Z., Sanada, K., Samuels, B.A., Shih, H., Tsai, L.H. Cell (2003) [Pubmed]
  5. Stereocilia defects in the sensory hair cells of the inner ear in mice deficient in integrin alpha8beta1. Littlewood Evans, A., Müller, U. Nat. Genet. (2000) [Pubmed]
  6. Focal adhesion kinase (p125FAK): a point of convergence in the action of neuropeptides, integrins, and oncogenes. Zachary, I., Rozengurt, E. Cell (1992) [Pubmed]
  7. Suppression of RhoA activity by focal adhesion kinase-induced activation of p190RhoGAP: role in regulation of endothelial permeability. Holinstat, M., Knezevic, N., Broman, M., Samarel, A.M., Malik, A.B., Mehta, D. J. Biol. Chem. (2006) [Pubmed]
  8. Hyperosmotic stress induces rapid focal adhesion kinase phosphorylation at tyrosines 397 and 577. Role of Src family kinases and Rho family GTPases. Lunn, J.A., Rozengurt, E. J. Biol. Chem. (2004) [Pubmed]
  9. Re-expression of the tumor suppressor NF2/merlin inhibits invasiveness in mesothelioma cells and negatively regulates FAK. Poulikakos, P.I., Xiao, G.H., Gallagher, R., Jablonski, S., Jhanwar, S.C., Testa, J.R. Oncogene (2006) [Pubmed]
  10. RNA interference targeting focal adhesion kinase enhances pancreatic adenocarcinoma gemcitabine chemosensitivity. Duxbury, M.S., Ito, H., Benoit, E., Zinner, M.J., Ashley, S.W., Whang, E.E. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  11. Inhibition of melanoma growth and metastasis by combination with (-)-epigallocatechin-3-gallate and dacarbazine in mice. Liu, J.D., Chen, S.H., Lin, C.L., Tsai, S.H., Liang, Y.C. J. Cell. Biochem. (2001) [Pubmed]
  12. Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. Schlaepfer, D.D., Hanks, S.K., Hunter, T., van der Geer, P. Nature (1994) [Pubmed]
  13. Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression. Zhao, J., Bian, Z.C., Yee, K., Chen, B.P., Chien, S., Guan, J.L. Mol. Cell (2003) [Pubmed]
  14. Induction of apoptosis after expression of PYK2, a tyrosine kinase structurally related to focal adhesion kinase. Xiong, W., Parsons, J.T. J. Cell Biol. (1997) [Pubmed]
  15. Control of axonal branching and synapse formation by focal adhesion kinase. Rico, B., Beggs, H.E., Schahin-Reed, D., Kimes, N., Schmidt, A., Reichardt, L.F. Nat. Neurosci. (2004) [Pubmed]
  16. Direct interaction of focal adhesion kinase with p190RhoGEF. Zhai, J., Lin, H., Nie, Z., Wu, J., Cañete-Soler, R., Schlaepfer, W.W., Schlaepfer, D.D. J. Biol. Chem. (2003) [Pubmed]
  17. Alterations in granule matrix and cell surface of focal adhesion kinase-deficient mast cells. Vial, D., Oliver, C., Jamur, M.C., Pastor, M.V., da Silva Trindade, E., Berenstein, E., Zhang, J., Siraganian, R.P. J. Immunol. (2003) [Pubmed]
  18. Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas. Polte, T.R., Hanks, S.K. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  19. Trichostatin A-induced detransformation correlates with decreased focal adhesion kinase phosphorylation at tyrosine 861 in ras-transformed fibroblasts. Lim, Y., Han, I., Kwon, H.J., Oh, E.S. J. Biol. Chem. (2002) [Pubmed]
  20. Different modes and qualities of tyrosine phosphorylation of Fak and Pyk2 during epithelial-mesenchymal transdifferentiation and cell migration: analysis of specific phosphorylation events using site-directed antibodies. Nakamura, K., Yano, H., Schaefer, E., Sabe, H. Oncogene (2001) [Pubmed]
  21. Mitogen-induced, FAK-dependent tyrosine phosphorylation of the SSeCKS scaffolding protein. Xia, W., Gelman, I.H. Exp. Cell Res. (2002) [Pubmed]
  22. Tumor necrosis factor-induced nuclear factor kappaB activation is impaired in focal adhesion kinase-deficient fibroblasts. Funakoshi-Tago, M., Sonoda, Y., Tanaka, S., Hashimoto, K., Tago, K., Tominaga, S., Kasahara, T. J. Biol. Chem. (2003) [Pubmed]
  23. Integrin-mediated activation of MAP kinase is independent of FAK: evidence for dual integrin signaling pathways in fibroblasts. Lin, T.H., Aplin, A.E., Shen, Y., Chen, Q., Schaller, M., Romer, L., Aukhil, I., Juliano, R.L. J. Cell Biol. (1997) [Pubmed]
  24. Src and FAK kinases cooperate to phosphorylate paxillin kinase linker, stimulate its focal adhesion localization, and regulate cell spreading and protrusiveness. Brown, M.C., Cary, L.A., Jamieson, J.S., Cooper, J.A., Turner, C.E. Mol. Biol. Cell (2005) [Pubmed]
  25. Signal transduction in confluent C3H 10T1/2 cells. The role of focal adhesion kinase. Miłoszewska, J., Trembacz, H., Janik, P. Acta Biochim. Pol. (2001) [Pubmed]
  26. Cdk5 phosphorylation of FAK regulates centrosome-associated miocrotubules and neuronal migration. Xie, Z., Tsai, L.H. Cell Cycle (2004) [Pubmed]
  27. Identification of Src-specific phosphorylation site on focal adhesion kinase: dissection of the role of Src SH2 and catalytic functions and their consequences for tumor cell behavior. Brunton, V.G., Avizienyte, E., Fincham, V.J., Serrels, B., Metcalf, C.A., Sawyer, T.K., Frame, M.C. Cancer Res. (2005) [Pubmed]
  28. 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. Owen, J.D., Ruest, P.J., Fry, D.W., Hanks, S.K. Mol. Cell. Biol. (1999) [Pubmed]
  29. Mechanical strain on osteoblasts activates autophosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 tyrosine sites involved in ERK activation. Boutahar, N., Guignandon, A., Vico, L., Lafage-Proust, M.H. J. Biol. Chem. (2004) [Pubmed]
  30. MEK kinase 1 interacts with focal adhesion kinase and regulates insulin receptor substrate-1 expression. Yujiri, T., Nawata, R., Takahashi, T., Sato, Y., Tanizawa, Y., Kitamura, T., Oka, Y. J. Biol. Chem. (2003) [Pubmed]
  31. Differentiation and transforming growth factor-beta receptor down-regulation by collagen-alpha2beta1 integrin interaction is mediated by focal adhesion kinase and its downstream signals in murine osteoblastic cells. Takeuchi, Y., Suzawa, M., Kikuchi, T., Nishida, E., Fujita, T., Matsumoto, T. J. Biol. Chem. (1997) [Pubmed]
  32. Vinculin modulation of paxillin-FAK interactions regulates ERK to control survival and motility. Subauste, M.C., Pertz, O., Adamson, E.D., Turner, C.E., Junger, S., Hahn, K.M. J. Cell Biol. (2004) [Pubmed]
  33. Defective Rac-mediated proliferation and survival after targeted mutation of the beta1 integrin cytodomain. Hirsch, E., Barberis, L., Brancaccio, M., Azzolino, O., Xu, D., Kyriakis, J.M., Silengo, L., Giancotti, F.G., Tarone, G., Fässler, R., Altruda, F. J. Cell Biol. (2002) [Pubmed]
  34. Gene Targeting of Cdc42 and Cdc42GAP Affirms the Critical Involvement of Cdc42 in Filopodia Induction, Directed Migration, and Proliferation in Primary Mouse Embryonic Fibroblasts. Yang, L., Wang, L., Zheng, Y. Mol. Biol. Cell (2006) [Pubmed]
  35. Focal adhesion kinase activated by beta(4) integrin ligation to mCLCA1 mediates early metastatic growth. Abdel-Ghany, M., Cheng, H.C., Elble, R.C., Pauli, B.U. J. Biol. Chem. (2002) [Pubmed]
  36. The association of ASAP1, an ADP ribosylation factor-GTPase activating protein, with focal adhesion kinase contributes to the process of focal adhesion assembly. Liu, Y., Loijens, J.C., Martin, K.H., Karginov, A.V., Parsons, J.T. Mol. Biol. Cell (2002) [Pubmed]
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