The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CSK  -  c-src tyrosine kinase

Homo sapiens

Synonyms: C-Src kinase, Protein-tyrosine kinase CYL, Tyrosine-protein kinase CSK
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CSK


High impact information on CSK


Chemical compound and disease context of CSK


Biological context of CSK


Anatomical context of CSK

  • In this study we have demonstrated that both CD44 (the hyaluronan (HA) receptor) and c-Src kinase are expressed in human ovarian tumor cells (SK-OV-3.ipl cell line), and that these two proteins are physically associated as a complex in vivo [1].
  • We also observed that fibroblasts stimulated with IGF-I or insulin showed a rapid and transient decrease in c-Src tyrosine kinase activity [14].
  • Northern blot analysis revealed a 2.2 kb transcript in various myeloid cell lines but not in adult tissues except for the brain and the lung, whereas CSK mRNA was ubiquitously expressed [11].
  • FAK associates with CSK 48 h after infection and recruits it to focal contacts [15].
  • De novo expression of pp125FAK in human macrophages regulates CSK distribution and MAP kinase activation but does not affect focal contact structure [15].

Associations of CSK with chemical compounds


Physical interactions of CSK

  • We show the high PAG-binding ability with CSK in vitro as well as the human PAG structure characterized by 11 alpha-helix structures including a 3 kDa transmembrane domain [19].
  • We show that in the early phases of cell adhesion integrins associate with EGF receptors on the cell membrane in a macromolecular complex including the adaptor protein p130Cas and the c-Src kinase, the latter being required for adhesion-dependent assembly of the macromolecular complex [20].
  • 3D-QSAR studies on c-Src kinase inhibitors and docking analyses of a potent dual kinase inhibitor of c-Src and c-Abl kinases [21].

Enzymatic interactions of CSK

  • We found that the SH2 domain of CSK binds to the tyrosine-phosphorylated form of IGF-IR and IR [14].
  • Under these in vitro conditions, E381G c-Src was found to be phosphorylated by CSK to wild-type levels, while E527K c-Src was not detectably phosphorylated [22].
  • In vivo S2V was tyrosine-phosphorylated when co-expressed with exogenous c-Src kinase [23].
  • Changing all of these sites to phenylalanine resulted in a villin mutant that neither was phosphorylated in TKX1 cells nor was a substrate for c-src kinase in an in vitro kinase assay [24].

Regulatory relationships of CSK


Other interactions of CSK

  • We observed that the IGF-IR and IR associated with the C-terminal Src kinase (CSK) following ligand stimulation [14].
  • Even though CD85j was detected in both anti-SHP1 and CSK immunoprecipitates, these two molecules did not co-precipitate together with CD85j [30].
  • Characterization of two activated mutants of human pp60c-src that escape c-Src kinase regulation by distinct mechanisms [22].
  • Unlike CSK, the SH3 domain of HYL was unique since the ALYDY motif was absent [11].
  • Sam68 is a 68 kDa protein that associates with and is phosphorylated by the c-Src kinase at mitosis [31].

Analytical, diagnostic and therapeutic context of CSK


  1. CD44 interaction with c-Src kinase promotes cortactin-mediated cytoskeleton function and hyaluronic acid-dependent ovarian tumor cell migration. Bourguignon, L.Y., Zhu, H., Shao, L., Chen, Y.W. J. Biol. Chem. (2001) [Pubmed]
  2. Tyrosine nitration of c-SRC tyrosine kinase in human pancreatic ductal adenocarcinoma. MacMillan-Crow, L.A., Greendorfer, J.S., Vickers, S.M., Thompson, J.A. Arch. Biochem. Biophys. (2000) [Pubmed]
  3. Cooperative action of tamoxifen and c-Src inhibition in preventing the growth of estrogen receptor-positive human breast cancer cells. Herynk, M.H., Beyer, A.R., Cui, Y., Weiss, H., Anderson, E., Green, T.P., Fuqua, S.A. Mol. Cancer Ther. (2006) [Pubmed]
  4. Expression of C-terminal src kinase in human colorectal cancer cell lines. Watanabe, N., Matsuda, S., Kuramochi, S., Tsuzuku, J., Yamamoto, T., Endo, K. Jpn. J. Clin. Oncol. (1995) [Pubmed]
  5. SRC regulates actin dynamics and invasion of malignant glial cells in three dimensions. Angers-Loustau, A., Hering, R., Werbowetski, T.E., Kaplan, D.R., Del Maestro, R.F. Mol. Cancer Res. (2004) [Pubmed]
  6. RhoD regulates endosome dynamics through Diaphanous-related Formin and Src tyrosine kinase. Gasman, S., Kalaidzidis, Y., Zerial, M. Nat. Cell Biol. (2003) [Pubmed]
  7. Elevated c-Src tyrosine kinase activity in premalignant epithelia of ulcerative colitis. Cartwright, C.A., Coad, C.A., Egbert, B.M. J. Clin. Invest. (1994) [Pubmed]
  8. Coupling of M2 muscarinic receptor to L-type Ca channel via c-src kinase in rabbit colonic circular smooth muscle. Jin, X., Morsy, N., Shoeb, F., Zavzavadjian, J., Akbarali, H.I. Gastroenterology (2002) [Pubmed]
  9. Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling. Johnsen, I.B., Nguyen, T.T., Ringdal, M., Tryggestad, A.M., Bakke, O., Lien, E., Espevik, T., Anthonsen, M.W. EMBO J. (2006) [Pubmed]
  10. Osteopontin induces AP-1-mediated secretion of urokinase-type plasminogen activator through c-Src-dependent epidermal growth factor receptor transactivation in breast cancer cells. Das, R., Mahabeleshwar, G.H., Kundu, G.C. J. Biol. Chem. (2004) [Pubmed]
  11. Molecular cloning of a novel non-receptor tyrosine kinase, HYL (hematopoietic consensus tyrosine-lacking kinase). Sakano, S., Iwama, A., Inazawa, J., Ariyama, T., Ohno, M., Suda, T. Oncogene (1994) [Pubmed]
  12. Characterization of mouse non-receptor tyrosine kinase gene, HYL. Hamaguchi, I., Iwama, A., Yamaguchi, N., Sakano, S., Matsuda, Y., Suda, T. Oncogene (1994) [Pubmed]
  13. Characterization of the human CSK locus. Bräuninger, A., Karn, T., Strebhardt, K., Rübsamen-Waigmann, H. Oncogene (1993) [Pubmed]
  14. C-terminal Src kinase associates with ligand-stimulated insulin-like growth factor-I receptor. Arbet-Engels, C., Tartare-Deckert, S., Eckhart, W. J. Biol. Chem. (1999) [Pubmed]
  15. De novo expression of pp125FAK in human macrophages regulates CSK distribution and MAP kinase activation but does not affect focal contact structure. De Nichilo, M.O., Katz, B.Z., O'Connell, B., Yamada, K.M. J. Cell. Physiol. (1999) [Pubmed]
  16. Biochemical and cellular effects of c-Src kinase-selective pyrido[2, 3-d]pyrimidine tyrosine kinase inhibitors. Kraker, A.J., Hartl, B.G., Amar, A.M., Barvian, M.R., Showalter, H.D., Moore, C.W. Biochem. Pharmacol. (2000) [Pubmed]
  17. Expression and subcellular distribution of the active form of c-Src tyrosine kinase in differentiating human endometrial stromal cells. Yamamoto, Y., Maruyama, T., Sakai, N., Sakurai, R., Shimizu, A., Hamatani, T., Masuda, H., Uchida, H., Sabe, H., Yoshimura, Y. Mol. Hum. Reprod. (2002) [Pubmed]
  18. The nonreceptor protein-tyrosine kinase CSK complexes directly with the GTPase-activating protein-associated p62 protein in cells expressing v-Src or activated c-Src. Neet, K., Hunter, T. Mol. Cell. Biol. (1995) [Pubmed]
  19. Expression and Purification of Human PAG, a Transmembrane Adapter Protein Using an Insect Cell Expression System and its Structure Basis. Takeuchi, S. Protein J. (2006) [Pubmed]
  20. Integrin-induced epidermal growth factor (EGF) receptor activation requires c-Src and p130Cas and leads to phosphorylation of specific EGF receptor tyrosines. Moro, L., Dolce, L., Cabodi, S., Bergatto, E., Erba, E.B., Smeriglio, M., Turco, E., Retta, S.F., Giuffrida, M.G., Venturino, M., Godovac-Zimmermann, J., Conti, A., Schaefer, E., Beguinot, L., Tacchetti, C., Gaggini, P., Silengo, L., Tarone, G., Defilippi, P. J. Biol. Chem. (2002) [Pubmed]
  21. 3D-QSAR studies on c-Src kinase inhibitors and docking analyses of a potent dual kinase inhibitor of c-Src and c-Abl kinases. Thaimattam, R., Daga, P.R., Banerjee, R., Iqbal, J. Bioorg. Med. Chem. (2005) [Pubmed]
  22. Characterization of two activated mutants of human pp60c-src that escape c-Src kinase regulation by distinct mechanisms. Bjorge, J.D., Bellagamba, C., Cheng, H.C., Tanaka, A., Wang, J.H., Fujita, D.J. J. Biol. Chem. (1995) [Pubmed]
  23. Identification and characterization of S2V, a novel putative siglec that contains two V set Ig-like domains and recruits protein-tyrosine phosphatases SHPs. Yu, Z., Lai, C.M., Maoui, M., Banville, D., Shen, S.H. J. Biol. Chem. (2001) [Pubmed]
  24. Regulation of actin dynamics by tyrosine phosphorylation: identification of tyrosine phosphorylation sites within the actin-severing domain of villin. Zhai, L., Kumar, N., Panebra, A., Zhao, P., Parrill, A.L., Khurana, S. Biochemistry (2002) [Pubmed]
  25. c-Src mediates mitogenic signals and associates with cytoskeletal proteins upon vascular endothelial growth factor stimulation in Kaposi's sarcoma cells. Munshi, N., Groopman, J.E., Gill, P.S., Ganju, R.K. J. Immunol. (2000) [Pubmed]
  26. Signal transduction through extracellular signal-regulated kinase-like pp57 blocked in differentiated colon carcinoma cells having low levels of c-src kinase. Lee, H., Hsu, S., Winawer, S., Friedman, E. J. Biol. Chem. (1993) [Pubmed]
  27. Induction of phospholipid hydroperoxide glutathione peroxidase in human polymorphonuclear neutrophils and HL60 cells stimulated with TNF-alpha. Hattori, H., Imai, H., Furuhama, K., Sato, O., Nakagawa, Y. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  28. Phosphopeptide occupancy and photoaffinity cross-linking of the v-Src SH2 domain attenuates tyrosine kinase activity. Garcia, P., Shoelson, S.E., Drew, J.S., Miller, W.T. J. Biol. Chem. (1994) [Pubmed]
  29. Analysis of the binding of the Src homology 2 domain of Csk to tyrosine-phosphorylated proteins in the suppression and mitotic activation of c-Src. Sabe, H., Hata, A., Okada, M., Nakagawa, H., Hanafusa, H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  30. Recruitment of C-terminal Src kinase by the leukocyte inhibitory receptor CD85j. Sayós, J., Martínez-Barriocanal, A., Kitzig, F., Bellón, T., López-Botet, M. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  31. Evidence for SH3 domain directed binding and phosphorylation of Sam68 by Src. Shen, Z., Batzer, A., Koehler, J.A., Polakis, P., Schlessinger, J., Lydon, N.B., Moran, M.F. Oncogene (1999) [Pubmed]
  32. The c-src tyrosine kinase (CSK) gene, a potential antioncogene, localizes to human chromosome region 15q23----q25. Armstrong, E., Cannizzaro, L., Bergman, M., Huebner, K., Alitalo, K. Cytogenet. Cell Genet. (1992) [Pubmed]
  33. Spleen protein tyrosine kinases TPK-IIB and CSK display different immunoreactivity and opposite specificities toward c-src-derived peptides. Brunati, A.M., Allee, G., Marin, O., Donella-Deana, A., Cesaro, L., Bougeret, C., Fagard, R., Benarous, R., Fischer, S., Pinna, L.A. FEBS Lett. (1992) [Pubmed]
  34. Rak, a novel nuclear tyrosine kinase expressed in epithelial cells. Cance, W.G., Craven, R.J., Bergman, M., Xu, L., Alitalo, K., Liu, E.T. Cell Growth Differ. (1994) [Pubmed]
WikiGenes - Universities