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Gene Review

PTK2  -  protein tyrosine kinase 2

Homo sapiens

Synonyms: FADK, FADK 1, FAK, FAK1, FRNK, ...
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Disease relevance of PTK2

  • PTK2 and EIF3S3 genes may be amplification targets at 8q23-q24 and are associated with large hepatocellular carcinomas [1].
  • When we analyzed potential relationships between elevated expression of PTK2 and EIF3S3 and clinicopathologic parameters, high expression of the 2 transcripts was significantly associated with large (>5 cm) tumor size and with hepatitis B virus (HBV) infection [1].
  • In this study, FAK protein expression and mRNA were detected in 25 of 60 cases (42%) of acute myeloid leukemia (AML) [2].
  • Furthermore, C8161 melanoma cells with endogenous CD151 were also shown to respond to homophilic CD151 interactions for the induction of adhesion-dependent activation of FAK, Src, and c-Jun [3].
  • Thus, FAK may act in glioblastoma as a downstream target of growth factor signaling, with integrins enhancing the impact of such signaling in the tumor microenvironment [4].

High impact information on PTK2

  • Further, HHV-8 infection induced the integrin-mediated activation of focal adhesion kinase (FAK) [5].
  • Overexpression of FAK partially antagonized the effects of PTEN [6].
  • Aggregation of integrins by noninhibitory monoclonal antibodies on beads induced intracellular accumulations of pp125FAK and tensin, as well as phosphorylation, but no accumulation of other cytoskeletal proteins such as talin [7].
  • As both FAK and Src catalytic activities are important in promoting VEGF-associated tumor angiogenesis and protease-associated tumor metastasis, support is growing that FAK and Src may be therapeutically relevant targets in the inhibition of tumor progression [8].
  • Integrins can alter cellular behavior through the recruitment and activation of signaling proteins such as non-receptor tyrosine kinases including focal adhesion kinase (FAK) and c-Src that form a dual kinase complex [8].

Chemical compound and disease context of PTK2


Biological context of PTK2


Anatomical context of PTK2

  • In conclusion, PTK2 and EIF3S3, which, respectively, encode focal adhesion kinase and the p40 subunit of the eukaryotic initiation factor 3, were probable targets within the amplification at 8q23-q24 and may be involved in progression of HCC [1].
  • The human homolog (PTK2) has been assigned to human Chr 8 on a panel of somatic hybrid cell lines [14].
  • Overexpression of dominant-negative FAK, FRNK, along with CIB in CHO cells completely inhibits CIB-induced cell migration [19].
  • Similar to FAK, dephosphorylation of RAFTK was observed when adherent transfected COS cells were detached [20].
  • Coexpression of RAFTK and FAK proteins in megakaryocytic cells and blood platelets was observed [20].

Associations of PTK2 with chemical compounds

  • Our results establish that FAK is an important receptor-proximal link between growth-factor-receptor and integrin signalling pathways [15].
  • The size of aggregates formed at a high shear rate in the presence of 2B-rVWF was decreased by genistein, demonstrating the biologic relevance of pp125FAK [21].
  • In contrast, neither RGDS peptide nor MoAb 7E3, both known to block alphaIIbbeta3 engagement, had any effect on SIPA and pp125FAK [21].
  • FAK+ AML cells displayed significantly higher migration capacities and resistance to daunorubicin, compared with FAK- cells [2].
  • Focal adhesion kinase (FAK) is phosphorylated on tyrosine and serine residues after cell activation [22].

Physical interactions of PTK2

  • Focal adhesion kinase interacts with the transcriptional coactivator FHL2 and both are overexpressed in epithelial ovarian cancer [23].
  • In addition, pp125FAK formed signalling complexes with both paxillin and p50csk in PC-3 cells as in metastatic PCa tissues [24].
  • PI 3-kinase has also been shown to bind FAK in a cell adhesion-dependent manner at the major autophosphorylation site Y397 [25].
  • The results demonstrate that tyrosine-phosphorylated pp125FAK directly interacts with the SH2 domain of Grb2 [26].
  • The PTEN trapping mutant D92A bound wild-type FAK, requiring FAK autophosphorylation site Tyr397 [27].

Enzymatic interactions of PTK2


Co-localisations of PTK2

  • A fraction of Nck-2 co-localizes with FAK at cell periphery in spreading cells [33].

Regulatory relationships of PTK2


Other interactions of PTK2


Analytical, diagnostic and therapeutic context of PTK2


  1. PTK2 and EIF3S3 genes may be amplification targets at 8q23-q24 and are associated with large hepatocellular carcinomas. Okamoto, H., Yasui, K., Zhao, C., Arii, S., Inazawa, J. Hepatology (2003) [Pubmed]
  2. Expression of focal adhesion kinase in acute myeloid leukemia is associated with enhanced blast migration, increased cellularity, and poor prognosis. Recher, C., Ysebaert, L., Beyne-Rauzy, O., Mansat-De Mas, V., Ruidavets, J.B., Cariven, P., Demur, C., Payrastre, B., Laurent, G., Racaud-Sultan, C. Cancer Res. (2004) [Pubmed]
  3. Homophilic interactions of Tetraspanin CD151 up-regulate motility and matrix metalloproteinase-9 expression of human melanoma cells through adhesion-dependent c-Jun activation signaling pathways. Hong, I.K., Jin, Y.J., Byun, H.J., Jeoung, D.I., Kim, Y.M., Lee, H. J. Biol. Chem. (2006) [Pubmed]
  4. In situ analysis of integrin and growth factor receptor signaling pathways in human glioblastomas suggests overlapping relationships with focal adhesion kinase activation. Riemenschneider, M.J., Mueller, W., Betensky, R.A., Mohapatra, G., Louis, D.N. Am. J. Pathol. (2005) [Pubmed]
  5. Integrin alpha3beta1 (CD 49c/29) is a cellular receptor for Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) entry into the target cells. Akula, S.M., Pramod, N.P., Wang, F.Z., Chandran, B. Cell (2002) [Pubmed]
  6. Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Tamura, M., Gu, J., Matsumoto, K., Aota, S., Parsons, R., Yamada, K.M. Science (1998) [Pubmed]
  7. Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function. Miyamoto, S., Akiyama, S.K., Yamada, K.M. Science (1995) [Pubmed]
  8. Integrin-regulated FAK-Src signaling in normal and cancer cells. Mitra, S.K., Schlaepfer, D.D. Curr. Opin. Cell Biol. (2006) [Pubmed]
  9. ERK1/2 and MEK1/2 induced by Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) early during infection of target cells are essential for expression of viral genes and for establishment of infection. Sharma-Walia, N., Krishnan, H.H., Naranatt, P.P., Zeng, L., Smith, M.S., Chandran, B. J. Virol. (2005) [Pubmed]
  10. Focal adhesion kinase and protein kinase B cooperate to suppress Doxorubicin-induced apoptosis of breast tumor cells. van Nimwegen, M.J., Huigsloot, M., Camier, A., Tijdens, I.B., van de Water, B. Mol. Pharmacol. (2006) [Pubmed]
  11. Garcinol modulates tyrosine phosphorylation of FAK and subsequently induces apoptosis through down-regulation of Src, ERK, and Akt survival signaling in human colon cancer cells. Liao, C.H., Sang, S., Ho, C.T., Lin, J.K. J. Cell. Biochem. (2005) [Pubmed]
  12. Expression of focal adhesion kinase (p125 FAK) and proline-rich tyrosine kinase 2 (PYK2/CAKb) in cerebral metastases, correlation with VEGF-R-, ecNOS III-labelling and morphometric data. Ludwig, H.C., Akhavan-Shigari, R., Rausch, S., Schallock, K., Quentin, C., Bockermann, V., Kolenda, H. Anticancer Res. (2000) [Pubmed]
  13. Human cytomegalovirus chemokine receptor US28-induced smooth muscle cell migration is mediated by focal adhesion kinase and Src. Streblow, D.N., Vomaske, J., Smith, P., Melnychuk, R., Hall, L., Pancheva, D., Smit, M., Casarosa, P., Schlaepfer, D.D., Nelson, J.A. J. Biol. Chem. (2003) [Pubmed]
  14. Mapping of the focal adhesion kinase (Fadk) gene to mouse chromosome 15 and human chromosome 8. Fiedorek, F.T., Kay, E.S. Mamm. Genome (1995) [Pubmed]
  15. FAK integrates growth-factor and integrin signals to promote cell migration. Sieg, D.J., Hauck, C.R., Ilic, D., Klingbeil, C.K., Schaefer, E., Damsky, C.H., Schlaepfer, D.D. Nat. Cell Biol. (2000) [Pubmed]
  16. Focal adhesion kinase and phospholipase C gamma involvement in adhesion and migration of human hepatic stellate cells. Carloni, V., Romanelli, R.G., Pinzani, M., Laffi, G., Gentilini, P. Gastroenterology (1997) [Pubmed]
  17. Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility. Mañes, S., Mira, E., Gómez-Mouton, C., Zhao, Z.J., Lacalle, R.A., Martínez-A, C. Mol. Cell. Biol. (1999) [Pubmed]
  18. Signaling through focal adhesion kinase. Schlaepfer, D.D., Hauck, C.R., Sieg, D.J. Prog. Biophys. Mol. Biol. (1999) [Pubmed]
  19. Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen. Naik, M.U., Naik, U.P. Blood (2003) [Pubmed]
  20. Characterization of RAFTK, a novel focal adhesion kinase, and its integrin-dependent phosphorylation and activation in megakaryocytes. Li, J., Avraham, H., Rogers, R.A., Raja, S., Avraham, S. Blood (1996) [Pubmed]
  21. Activation of pp125FAK by type 2B recombinant von Willebrand factor binding to platelet GPIb at a high shear rate occurs independently of alpha IIb beta 3 engagement. Mekrache, M., Bachelot-Loza, C., Ajzenberg, N., Saci, A., Legendre, P., Baruch, D. Blood (2003) [Pubmed]
  22. Phosphorylation of focal adhesion kinase (FAK) on Ser732 is induced by rho-dependent kinase and is essential for proline-rich tyrosine kinase-2-mediated phosphorylation of FAK on Tyr407 in response to vascular endothelial growth factor. Le Boeuf, F., Houle, F., Sussman, M., Huot, J. Mol. Biol. Cell (2006) [Pubmed]
  23. Focal adhesion kinase interacts with the transcriptional coactivator FHL2 and both are overexpressed in epithelial ovarian cancer. Gabriel, B., Mildenberger, S., Weisser, C.W., Metzger, E., Gitsch, G., Schüle, R., Müller, J.M. Anticancer Res. (2004) [Pubmed]
  24. Focal adhesion kinase (pp125FAK) expression, activation and association with paxillin and p50CSK in human metastatic prostate carcinoma. Tremblay, L., Hauck, W., Aprikian, A.G., Begin, L.R., Chapdelaine, A., Chevalier, S. Int. J. Cancer (1996) [Pubmed]
  25. Role of focal adhesion kinase in integrin signaling. Guan, J.L. Int. J. Biochem. Cell Biol. (1997) [Pubmed]
  26. Stimulation of human monocytes with macrophage colony-stimulating factor induces a Grb2-mediated association of the focal adhesion kinase pp125FAK and dynamin. Kharbanda, S., Saleem, A., Yuan, Z., Emoto, Y., Prasad, K.V., Kufe, D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  27. PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway. Tamura, M., Gu, J., Danen, E.H., Takino, T., Miyamoto, S., Yamada, K.M. J. Biol. Chem. (1999) [Pubmed]
  28. Tumor suppressor PTEN inhibits integrin- and growth factor-mediated mitogen-activated protein (MAP) kinase signaling pathways. Gu, J., Tamura, M., Yamada, K.M. J. Cell Biol. (1998) [Pubmed]
  29. Direct phosphorylation of proliferative and survival pathway proteins by RET. Panta, G.R., Du, L., Nwariaku, F.E., Kim, L.T. Surgery (2005) [Pubmed]
  30. A scaffold protein in the c-Jun N-terminal kinase signaling pathway is associated with focal adhesion kinase and tyrosine-phosphorylated. Takino, T., Yoshioka, K., Miyamori, H., Yamada, K.M., Sato, H. Oncogene (2002) [Pubmed]
  31. Interaction of Hic-5, A senescence-related protein, with focal adhesion kinase. Fujita, H., Kamiguchi, K., Cho, D., Shibanuma, M., Morimoto, C., Tachibana, K. J. Biol. Chem. (1998) [Pubmed]
  32. Characterization of morphological and cytoskeletal changes in trophoblast cells induced by insulin-like growth factor-I. Kabir-Salmani, M., Shiokawa, S., Akimoto, Y., Hasan-Nejad, H., Sakai, K., Nagamatsu, S., Sakai, K., Nakamura, Y., Hosseini, A., Iwashita, M. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  33. Nck-2 interacts with focal adhesion kinase and modulates cell motility. Goicoechea, S.M., Tu, Y., Hua, Y., Chen, K., Shen, T.L., Guan, J.L., Wu, C. Int. J. Biochem. Cell Biol. (2002) [Pubmed]
  34. Melanoma chondroitin sulfate proteoglycan enhances FAK and ERK activation by distinct mechanisms. Yang, J., Price, M.A., Neudauer, C.L., Wilson, C., Ferrone, S., Xia, H., Iida, J., Simpson, M.A., McCarthy, J.B. J. Cell Biol. (2004) [Pubmed]
  35. MAP-kinase activity necessary for TGFbeta1-stimulated mesangial cell type I collagen expression requires adhesion-dependent phosphorylation of FAK tyrosine 397. Hayashida, T., Wu, M.H., Pierce, A., Poncelet, A.C., Varga, J., Schnaper, H.W. J. Cell. Sci. (2007) [Pubmed]
  36. Characterization of signal transduction pathways in human bone marrow endothelial cells. Liu, Z.Y., Ganju, R.K., Wang, J.F., Schweitzer, K., Weksler, B., Avraham, S., Groopman, J.E. Blood (1997) [Pubmed]
  37. Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly. Zhao, Z.S., Manser, E., Loo, T.H., Lim, L. Mol. Cell. Biol. (2000) [Pubmed]
  38. Paxillin binding to the alpha 4 integrin subunit stimulates LFA-1 (integrin alpha L beta 2)-dependent T cell migration by augmenting the activation of focal adhesion kinase/proline-rich tyrosine kinase-2. Rose, D.M., Liu, S., Woodside, D.G., Han, J., Schlaepfer, D.D., Ginsberg, M.H. J. Immunol. (2003) [Pubmed]
  39. PRL-1 tyrosine phosphatase regulates c-Src levels, adherence, and invasion in human lung cancer cells. Achiwa, H., Lazo, J.S. Cancer Res. (2007) [Pubmed]
  40. Focal adhesion kinase activates Stat1 in integrin-mediated cell migration and adhesion. Xie, B., Zhao, J., Kitagawa, M., Durbin, J., Madri, J.A., Guan, J.L., Fu, X.Y. J. Biol. Chem. (2001) [Pubmed]
  41. Angiotensin II induces focal adhesion kinase/paxillin phosphorylation and cell migration in human umbilical vein endothelial cells. Montiel, M., de la Blanca, E.P., Jiménez, E. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  42. Activator protein 1 activation following hypoosmotic stress in HepG2 cells is actin cytoskeleton dependent. Kim, R.D., Darling, C.E., Roth, T.P., Ricciardi, R., Chari, R.S. J. Surg. Res. (2001) [Pubmed]
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