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Gene Review

Ptk2  -  protein tyrosine kinase 2

Rattus norvegicus

Synonyms: FADK 1, FAK, FRNK, Fak, Fak1, ...
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Disease relevance of Ptk2


Psychiatry related information on Ptk2


High impact information on Ptk2


Chemical compound and disease context of Ptk2

  • In OGD conditions, a preconditioning application of dexmedetomidine (0.2 microm, 20-min application, 3 h before anoxia) significantly reduced neuronal death and cleaved caspase-3 expression and significantly attenuated the decrease in phosphorylated FAK content [9].
  • CONCLUSIONS: In contrast to divalent cations, extracellular pressure may increase integrin affinity and promote colon cancer adhesion via actin dependent inside-out FAK and Src signals [8].
  • To study the role of FAK in breast tumor growth and metastasis formation, we used conditional doxycycline-regulated expression of a dominant-negative acting splice variant of FAK, FAK-related non-kinase (FRNK), in MTLn3 mammary adenocarcinoma cells in a syngeneic Fischer 344 rat tumor and metastasis model [10].
  • An enhanced tyrosine phosphorylation of FAK elicited by agonist occupancy of phospholipase C-coupled receptors (muscarinic cholinergic in SH-SY5Y neuroblastoma or bradykinin in PC12 cells) was blocked completely by wortmannin [11].

Biological context of Ptk2


Anatomical context of Ptk2

  • We compared CADTK regulation with that of the highly homologous focal adhesion tyrosine kinase (FAK) [16].
  • Disruption of the actin cytoskeleton was followed by a decrease in the membrane-associated pool of FAK, but not of PYK2 [13].
  • To further elucidate the regulation of FAK and PYK2 in nervous tissue, we investigated their distribution in brain subcellular fractions and analysed their translocation between membrane and cytosolic compartments [13].
  • In hippocampal neurons in culture at early stages of development, FAK+ and PYK2/CAKbeta were enriched in the perikarya and growth cones [17].
  • FAK+ and PYK2/CAKbeta, two related tyrosine kinases highly expressed in the central nervous system: similarities and differences in the expression pattern [17].

Associations of Ptk2 with chemical compounds

  • However, FRNK expression did not alter the magnitude or dynamics of ERK activation induced by PDGF-BB or angiotensin II [18].
  • Furthermore, the inhibition of Skp-2 expression by dominant negative FAK was reversed by the proteasome inhibitor MG-132 [12].
  • In intact nerve terminals, inhibition of Src kinases inhibited the membrane association of FAK, but not of PYK2, whereas tyrosine phosphatase inhibition sharply increased the membrane association of both FAK and PYK2 [13].
  • FAK phosphorylation by ET-1 was inhibited by cytochalasin D, lovastatin and Y-27632, but not by PD98059 or PP-2 [14].
  • Y-27632 (10 micromol/l; 1 h pretreatment), an inhibitor of Rho-associated coiled-coil-containing protein kinases (ROCK), prevented ET- and caPKC epsilon-induced FAK activation as well as cofilin phosphorylation [1].

Physical interactions of Ptk2

  • Indeed, the formation of p-FAK/c-Src protein complex, but not their association with beta1-integrin, was stimulated during T suppression-induced germ cell loss [19].
  • However, increases in contractile activity induced by increasing calcium concentration in the perfusate (from 0.5 to 5 mM) did not activate the FAK multicomponent signaling complex or ERK1/2 in the myocardium [20].

Regulatory relationships of Ptk2


Other interactions of Ptk2

  • Importantly, constitutively active Rac1 rescued the proliferation defects in FRNK expressing cells [18].
  • In rat hippocampal slices, FAK+ and PYK2/CAKbeta are differentially regulated by neurotransmitters and depolarization [17].
  • Such differential response of FAK to NGF and EGF may shape the specificity by which these growth factors control the status of cell-matrix adhesion and the adhesion-driven signaling [15].
  • Concomitantly a decreased association of FAK with its investigated molecular partners, Src kinase and p130Cas protein has been observed [2].
  • Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase thought to play a major role in transducing extracellular matrix (ECM)-derived survival signals into cells [2].

Analytical, diagnostic and therapeutic context of Ptk2

  • FAK activation was assessed by Western blot analysis with an antibody specific for FAK autophosphorylated at Y397 (Y397pFAK) [1].
  • Immunocytochemistry of the adult brain showed a widespread neuronal distribution of FAK+ and PYK2/CAKbeta immunoreactivities (ir) [17].
  • The pattern of expression of the multiple forms of FAK was studied by RT-PCR and Southern hybridization with specific primers and probes [24].
  • Dissection of PP1delta indicated 194-260 as the shortest FAK-interacting domain among those tested [25].
  • The PP1 eluted from a GST-FRNK affinity column displayed Mr of 35,000 when analyzed by gel-filtration on FPLC Superose 12, indicating the presence of an isolated PP1 catalytic subunit [25].


  1. Activation of focal adhesion kinase by protein kinase C epsilon in neonatal rat ventricular myocytes. Heidkamp, M.C., Bayer, A.L., Scully, B.T., Eble, D.M., Samarel, A.M. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  2. Neonatal cerebral hypoxia-ischemia: involvement of FAK-dependent pathway. Zalewska, T., Makarewicz, D., Janik, B., Ziemka-Nałecz, M. Int. J. Dev. Neurosci. (2005) [Pubmed]
  3. RhoA/ROCK signaling is critical to FAK activation by cyclic stretch in cardiac myocytes. Torsoni, A.S., Marin, T.M., Velloso, L.A., Franchini, K.G. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  4. Subcellular redistribution of focal adhesion kinase and its related nonkinase in hypertrophic myocardium. Yi, X.P., Wang, X., Gerdes, A.M., Li, F. Hypertension (2003) [Pubmed]
  5. Differential regulation of FAK and PYK2 tyrosine phosphorylation after electroconvulsive shock in the rat brain. Kang, U.G., Jun, S.J., Yoon, S.C., Jeon, S., Park, J.B., Chung, C.K., Juhnn, Y.S., Kim, Y.S. Neurosci. Lett. (2004) [Pubmed]
  6. Regulation of a neuronal form of focal adhesion kinase by anandamide. Derkinderen, P., Toutant, M., Burgaya, F., Le Bert, M., Siciliano, J.C., de Franciscis, V., Gelman, M., Girault, J.A. Science (1996) [Pubmed]
  7. Pyk2 and FAK regulate neurite outgrowth induced by growth factors and integrins. Ivankovic-Dikic, I., Grönroos, E., Blaukat, A., Barth, B.U., Dikic, I. Nat. Cell Biol. (2000) [Pubmed]
  8. Pressure activates colon cancer cell adhesion by inside-out focal adhesion complex and actin cytoskeletal signaling. Thamilselvan, V., Basson, M.D. Gastroenterology (2004) [Pubmed]
  9. Effects of dexmedetomidine on hippocampal focal adhesion kinase tyrosine phosphorylation in physiologic and ischemic conditions. Dahmani, S., Rouelle, D., Gressens, P., Mantz, J. Anesthesiology (2005) [Pubmed]
  10. Requirement for focal adhesion kinase in the early phase of mammary adenocarcinoma lung metastasis formation. van Nimwegen, M.J., Verkoeijen, S., van Buren, L., Burg, D., van de Water, B. Cancer Res. (2005) [Pubmed]
  11. Attenuation of focal adhesion kinase signaling following depletion of agonist-sensitive pools of phosphatidylinositol 4,5-bisphosphate. Linseman, D.A., Sorensen, S.D., Fisher, S.K. J. Neurochem. (1999) [Pubmed]
  12. Focal adhesion kinase (FAK)-dependent regulation of S-phase kinase-associated protein-2 (Skp-2) stability. A novel mechanism regulating smooth muscle cell proliferation. Bond, M., Sala-Newby, G.B., Newby, A.C. J. Biol. Chem. (2004) [Pubmed]
  13. The translocation of focal adhesion kinase in brain synaptosomes is regulated by phosphorylation and actin assembly. Bongiorno-Borbone, L., Onofri, F., Giovedì, S., Ferrari, R., Girault, J.A., Benfenati, F. J. Neurochem. (2002) [Pubmed]
  14. Focal adhesion kinase mediates endothelin-induced cyclin D3 expression in rat cultured astrocytes. Koyama, Y., Yoshioka, Y., Shinde, M., Matsuda, T., Baba, A. J. Neurochem. (2004) [Pubmed]
  15. Nerve growth factor (NGF) induces a rapid and sustained downregulation of the focal adhesion kinase (FAK). Gatti, A. Cell. Mol. Neurobiol. (2004) [Pubmed]
  16. Interactions between two cytoskeleton-associated tyrosine kinases: calcium-dependent tyrosine kinase and focal adhesion tyrosine kinase. Li, X., Dy, R.C., Cance, W.G., Graves, L.M., Earp, H.S. J. Biol. Chem. (1999) [Pubmed]
  17. FAK+ and PYK2/CAKbeta, two related tyrosine kinases highly expressed in the central nervous system: similarities and differences in the expression pattern. Menegon, A., Burgaya, F., Baudot, P., Dunlap, D.D., Girault, J.A., Valtorta, F. Eur. J. Neurosci. (1999) [Pubmed]
  18. An endogenous inhibitor of focal adhesion kinase blocks Rac1/JNK but not Ras/ERK-dependent signaling in vascular smooth muscle cells. Sundberg, L.J., Galante, L.M., Bill, H.M., Mack, C.P., Taylor, J.M. J. Biol. Chem. (2003) [Pubmed]
  19. Regulation of ectoplasmic specialization dynamics in the seminiferous epithelium by focal adhesion-associated proteins in testosterone-suppressed rat testes. Wong, C.H., Xia, W., Lee, N.P., Mruk, D.D., Lee, W.M., Cheng, C.Y. Endocrinology (2005) [Pubmed]
  20. Load-induced focal adhesion kinase activation in the myocardium: role of stretch and contractile activity. Domingos, P.P., Fonseca, P.M., Nadruz, W., Franchini, K.G. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  21. Integrin-mediated cell adhesion promotes tyrosine phosphorylation of p130Cas, a Src homology 3-containing molecule having multiple Src homology 2-binding motifs. Nojima, Y., Morino, N., Mimura, T., Hamasaki, K., Furuya, H., Sakai, R., Sato, T., Tachibana, K., Morimoto, C., Yazaki, Y. J. Biol. Chem. (1995) [Pubmed]
  22. Role of protein-tyrosine phosphatase SHP2 in focal adhesion kinase down-regulation during neutrophil cathepsin G-induced cardiomyocytes anoikis. Rafiq, K., Kolpakov, M.A., Abdelfettah, M., Streblow, D.N., Hassid, A., Dell'Italia, L.J., Sabri, A. J. Biol. Chem. (2006) [Pubmed]
  23. The interaction of activated integrin lymphocyte function-associated antigen 1 with ligand intercellular adhesion molecule 1 induces activation and redistribution of focal adhesion kinase and proline-rich tyrosine kinase 2 in T lymphocytes. Rodríguez-Fernández, J.L., Gómez, M., Luque, A., Hogg, N., Sánchez-Madrid, F., Cabañas, C. Mol. Biol. Cell (1999) [Pubmed]
  24. Cloning of focal adhesion kinase, pp125FAK, from rat brain reveals multiple transcripts with different patterns of expression. Burgaya, F., Girault, J.A. Brain Res. Mol. Brain Res. (1996) [Pubmed]
  25. Reciprocally interacting domains of protein phosphatase 1 and focal adhesion kinase. Bianchi, M., De Lucchini, S., Vietri, M., Villa-Moruzzi, E. Mol. Cell. Biochem. (2005) [Pubmed]
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