Gene Symbol: Csk
Description: C-terminal Src kinase
Alias: tyrosine-protein kinase CSK, C-SRC kinase, CSK, non-receptor tyrosine kinase, c-src tyrosine kinase, protein-tyrosine kinase (CSK)
Species: rat
Products:     Csk

Top Publications

  1. Okada M, Nada S, Yamanashi Y, Yamamoto T, Nakagawa H. CSK: a protein-tyrosine kinase involved in regulation of src family kinases. J Biol Chem. 1991;266:24249-52 pubmed
    ..Recently we have purified and cloned a protein-tyrosine kinase (designated as CSK) that can specifically phosphorylate the negative regulatory site of p60c-src...
  2. Cloutier J, Veillette A. Association of inhibitory tyrosine protein kinase p50csk with protein tyrosine phosphatase PEP in T cells and other hemopoietic cells. EMBO J. 1996;15:4909-18 pubmed
    p50csk is a tyrosine protein kinase (TPK) that represses the activity of Src family TPKs. We previously showed that Csk is a potent negative regulator of antigen receptor signaling in T lymphocytes and that its Src homology (SH) 3 and ..
  3. Ogawa A, Takayama Y, Sakai H, Chong K, Takeuchi S, Nakagawa A, et al. Structure of the carboxyl-terminal Src kinase, Csk. J Biol Chem. 2002;277:14351-4 pubmed
    The carboxyl-terminal Src kinase (Csk) is an indispensable negative regulator for the Src family tyrosine kinases (SFKs) that play pivotal roles in various cell signalings...
  4. Kawabuchi M, Satomi Y, Takao T, Shimonishi Y, Nada S, Nagai K, et al. Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases. Nature. 2000;404:999-1003 pubmed
    ..The activity of Src-PTKs in cells of different types is negatively controlled by Csk, which specifically phosphorylates a conserved regulatory tyrosine residue at the carboxy-terminal tail of the Src-..
  5. González Sánchez A, Jaraíz Rodríguez M, Domínguez Prieto M, Herrero González S, Medina J, Tabernero A. Connexin43 recruits PTEN and Csk to inhibit c-Src activity in glioma cells and astrocytes. Oncotarget. 2016;7:49819-49833 pubmed publisher
    ..The inhibition of c-Src requires phosphorylation at tyrosine 527 mediated by C-terminal Src kinase (Csk) and dephosphorylation at tyrosine 416 mediated by phosphatases, such as phosphatase and tensin homolog (PTEN)...
  6. Sarmiento J, Wallis R, Ning T, Marandi L, Chao G, Veillette A, et al. A functional polymorphism of Ptpn22 is associated with type 1 diabetes in the BioBreeding rat. J Immunol. 2015;194:615-29 pubmed publisher
    ..These findings are consistent with a role for rat Ptpn22 allelic variation within Iddm26.2 in the regulation of T cell responses, and subsequently the risk for development of T1D. ..
  7. Barlaam B, Fennell M, Germain H, Green T, Hennequin L, Morgentin R, et al. New heterocyclic analogues of 4-(2-chloro-5-methoxyanilino)quinazolines as potent and selective c-Src kinase inhibitors. Bioorg Med Chem Lett. 2005;15:5446-9 pubmed
    ..1muM inhibitors in a c-Src-driven cell proliferation assay and displayed adequate rat pharmacokinetics after oral administration. ..
  8. Kunte D, Wali R, Koetsier J, Hart J, Kostjukova M, Kilimnik A, et al. Down-regulation of the tumor suppressor gene C-terminal Src kinase: an early event during premalignant colonic epithelial hyperproliferation. FEBS Lett. 2005;579:3497-502 pubmed
    ..lesions in the azoxymethane-rat model of colon carcinogenesis; the tumor suppressor gene C-terminal Src kinase (Csk) was down-regulated with a concomitant increase in Src activity...
  9. Wang B, Lemay S, Tsai S, Veillette A. SH2 domain-mediated interaction of inhibitory protein tyrosine kinase Csk with protein tyrosine phosphatase-HSCF. Mol Cell Biol. 2001;21:1077-88 pubmed
    The protein tyrosine kinase (PTK) Csk is a potent negative regulator of several signal transduction processes, as a consequence of its exquisite ability to inactivate Src-related PTKs...

More Information


  1. Levinson N, Visperas P, Kuriyan J. The tyrosine kinase Csk dimerizes through Its SH3 domain. PLoS ONE. 2009;4:e7683 pubmed publisher
    ..The latter modification is achieved by the tyrosine kinase Csk (C-terminal Src Kinase), but the complete inactivation of the Src family kinases also requires the ..
  2. Seng S, Avraham H, Jiang S, Venkatesh S, Avraham S. KLHL1/MRP2 mediates neurite outgrowth in a glycogen synthase kinase 3beta-dependent manner. Mol Cell Biol. 2006;26:8371-84 pubmed
    ..Thus, this study provides, for the first time, insights into the involvement of MRP2 in neurite outgrowth, which occurs in a GSK3beta-dependent manner. ..
  3. Masaki T, Okada M, Tokuda M, Shiratori Y, Hatase O, Shirai M, et al. Reduced C-terminal Src kinase (Csk) activities in hepatocellular carcinoma. Hepatology. 1999;29:379-84 pubmed
    ..However, the mechanisms involved in this process remain unknown. C-terminal Src kinase (Csk) is a novel cytoplasmic protein tyrosine kinase that inactivates the members of the Src family protein tyrosine ..
  4. Matsuoka H, Nada S, Okada M. Mechanism of Csk-mediated down-regulation of Src family tyrosine kinases in epidermal growth factor signaling. J Biol Chem. 2004;279:5975-83 pubmed
    ..The function of SFK is regulated by phosphorylation at the C-terminal regulatory site mediated by Csk. Recently a novel SFK target Cbp (or PAG) was identified as a membrane-anchored scaffold protein for Csk...
  5. Ia K, Jeschke G, Deng Y, Kamaruddin M, Williamson N, Scanlon D, et al. Defining the substrate specificity determinants recognized by the active site of C-terminal Src kinase-homologous kinase (CHK) and identification of ?-synuclein as a potential CHK physiological substrate. Biochemistry. 2011;50:6667-77 pubmed publisher
    ..Thus, besides assisting in the identification of potential CHK physiological substrates, our findings shed new light on how CHK recognizes SFKs and other protein substrates. ..
  6. Tanaka H, Akagi K, Oneyama C, Tanaka M, Sasaki Y, Kanou T, et al. Identification of a new interaction mode between the Src homology 2 domain of C-terminal Src kinase (Csk) and Csk-binding protein/phosphoprotein associated with glycosphingolipid microdomains. J Biol Chem. 2013;288:15240-54 pubmed publisher
    ..Here, we report the solution structure of the SH2 domain of C-terminal Src kinase (Csk) in complex with a longer phosphopeptide from the Csk-binding protein (Cbp)...
  7. Dondog E. Functional modification of a murine macrophage cell line, J744A.1, transfected with rat csk genes. Hokkaido Igaku Zasshi. 2000;75:197-208 pubmed
    In a previous study of this laboratory, a macrophage cell line, J774A.1, transfected with rat csk gene and overexpressing the Csk proteins has been established...
  8. Honda Z, Suzuki T, Hirose N, Aihara M, Shimizu T, Nada S, et al. Roles of C-terminal Src kinase in the initiation and the termination of the high affinity IgE receptor-mediated signaling. J Biol Chem. 1997;272:25753-60 pubmed
    As an attempt to analyze the roles of C-terminal Src kinase (Csk) in the high affinity IgE receptor (FcepsilonRI)-mediated signaling, we overexpressed Csk, a membrane-targeted form of Csk (mCsk), and a kinase-defective, membrane-targeted ..
  9. Safari F, Murata Kamiya N, Saito Y, Hatakeyama M. Mammalian Pragmin regulates Src family kinases via the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif that is exploited by bacterial effectors. Proc Natl Acad Sci U S A. 2011;108:14938-43 pubmed publisher
    ..EPIYA motif by SFKs and thereby acquires the ability to interact with the SH2 domain of the C-terminal Src kinase (Csk), a negative regulator of SFKs...
  10. Colognato H, Ramachandrappa S, Olsen I, Ffrench Constant C. Integrins direct Src family kinases to regulate distinct phases of oligodendrocyte development. J Cell Biol. 2004;167:365-75 pubmed
    ..by different mechanisms: Lyn, by increased autophosphorylation of a catalytic tyrosine; and Fyn, by reduced Csk phosphorylation of the inhibitory COOH-terminal tyrosine...
  11. Inomata M, Takayama Y, Kiyama H, Nada S, Okada M, Nakagawa H. Regulation of Src family kinases in the developing rat brain: correlation with their regulator kinase, Csk. J Biochem. 1994;116:386-92 pubmed
    ..that the functions of Src family protein-tyrosine kinases are under the control of their regulator kinase, Csk. To evaluate the role of Csk-mediated regulation in neural tissues, we examined the correlation between the ..
  12. Zhang L, Ren Z, Yang Q, Ding G. Csk regulates angiotensin II-induced podocyte apoptosis. Apoptosis. 2016;21:846-55 pubmed publisher
    ..The mechanism underlying Ang II-induced podocyte apoptosis has not been established. C-terminal Src kinase (Csk) is a cytoplasmic kinase that interacts with scaffolding proteins involved in cell growth, adhesion, and ..
  13. Thomas R, Schmedt C, Novelli M, Choi B, Skok J, Tarakhovsky A, et al. C-terminal SRC kinase controls acute inflammation and granulocyte adhesion. Immunity. 2004;20:181-91 pubmed
    To establish whether the widely expressed regulator of Src family kinases Csk contributes to the control of acute inflammation in vivo, we inactivated csk in granulocytes by conditional mutagenesis (Cre/loxP)...
  14. Takayanagi H, Juji T, Miyazaki T, Iizuka H, Takahashi T, Isshiki M, et al. Suppression of arthritic bone destruction by adenovirus-mediated csk gene transfer to synoviocytes and osteoclasts. J Clin Invest. 1999;104:137-46 pubmed
    ..We constructed an adenovirus vector carrying the csk gene, which negatively regulates Src family tyrosine kinases...
  15. Obata Y, Fukumoto Y, Nakayama Y, Kuga T, Dohmae N, Yamaguchi N. The Lyn kinase C-lobe mediates Golgi export of Lyn through conformation-dependent ACSL3 association. J Cell Sci. 2010;123:2649-62 pubmed publisher
    ..Formation of a closed conformation by CSK prevents Lyn from associating with ACSL3, resulting in blockade of Lyn export from the Golgi...
  16. Nada S, Okada M, Macauley A, Cooper J, Nakagawa H. Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src. Nature. 1991;351:69-72 pubmed
    ..These results suggest that this protein-tyrosine kinase, which might negatively regulate p60c-src, represents a new type of tyrosine kinase. ..
  17. Saito K, Enya K, Oneyama C, Hikita T, Okada M. Proteomic identification of ZO-1/2 as a novel scaffold for Src/Csk regulatory circuit. Biochem Biophys Res Commun. 2008;366:969-75 pubmed
    ..a proteomic analysis of tyrosine phosphorylated proteins that interact with c-Src and/or its negative regulator Csk. The c-Src interacting proteins were affinity-purified from Src transformed cells using the Src SH2 domain as a ..
  18. Bougeret C, Rothhut B, Jullien P, Fischer S, Benarous R. Recombinant Csk expressed in Escherichia coli is autophosphorylated on tyrosine residue(s). Oncogene. 1993;8:1241-7 pubmed
    The C-terminal src kinase (Csk) is responsible for the phosphorylation of the carboxy-terminal tyrosine of several tyrosine kinases of the Src family. This phosphorylation site has a negative regulatory function...
  19. Baumeister U, Funke R, Ebnet K, Vorschmitt H, Koch S, Vestweber D. Association of Csk to VE-cadherin and inhibition of cell proliferation. EMBO J. 2005;24:1686-95 pubmed
    ..for proteins that could be involved in VE-cadherin signaling, we found the cytosolic C-terminal Src kinase (Csk), a negative regulator of Src family kinases...
  20. Ruppelt A, Mosenden R, Grönholm M, Aandahl E, Tobin D, Carlson C, et al. Inhibition of T cell activation by cyclic adenosine 5'-monophosphate requires lipid raft targeting of protein kinase A type I by the A-kinase anchoring protein ezrin. J Immunol. 2007;179:5159-68 pubmed
    ..by activation of type I protein kinase A (PKA), which in turn phosphorylates and activates C-terminal Src kinase (Csk) in T cell lipid rafts...
  21. Harita Y, Kurihara H, Kosako H, Tezuka T, Sekine T, Igarashi T, et al. Neph1, a component of the kidney slit diaphragm, is tyrosine-phosphorylated by the Src family tyrosine kinase and modulates intracellular signaling by binding to Grb2. J Biol Chem. 2008;283:9177-86 pubmed publisher
    ..using rat glomerular lysates, Neph1 but not nephrin specifically binds to adaptor protein Grb2 and tyrosine kinase Csk in a phosphorylation-dependent manner. Both tyrosine 637 and 638 of Neph1 are crucial for Neph1-Grb2 binding...
  22. Liu J, Shimosawa T, Matsui H, Meng F, Supowit S, Dipette D, et al. Adrenomedullin inhibits angiotensin II-induced oxidative stress via Csk-mediated inhibition of Src activity. Am J Physiol Heart Circ Physiol. 2007;292:H1714-21 pubmed
    ..Moreover, AM intersected ANG II signaling by inducing COOH-terminal Src kinase (Csk) activation that, in turn, inhibits Src activation...
  23. Georgakopoulos A, Litterst C, Ghersi E, Baki L, Xu C, Serban G, et al. Metalloproteinase/Presenilin1 processing of ephrinB regulates EphB-induced Src phosphorylation and signaling. EMBO J. 2006;25:1242-52 pubmed
    ..This peptide binds Src and inhibits its association with inhibitory kinase Csk, allowing autophosphorylation of Src at residue tyr418...
  24. Dey N, Howell B, De P, Durden D. CSK negatively regulates nerve growth factor induced neural differentiation and augments AKT kinase activity. Exp Cell Res. 2005;307:1-14 pubmed
    ..kinases (SFKs) is controlled by phosphorylation at their C-terminal 527-tyrosine residue by C-terminal SRC kinase, CSK. There is a paucity of information regarding the role of CSK and/or specific Src family kinases in neuronal ..
  25. Melendez J, Turner C, Avraham H, Steinberg S, Schaefer E, Sussman M. Cardiomyocyte apoptosis triggered by RAFTK/pyk2 via Src kinase is antagonized by paxillin. J Biol Chem. 2004;279:53516-23 pubmed
    ..of apoptosis using caspase-3 inhibitor IV (caspase-3 specific inhibitor), PP2 (Src-specific kinase inhibitor), or Csk (cellular negative regulator for Src), as well as dominant negative constructs for p38beta or MKP-1...
  26. Brdicka T, Pavlistová D, Leo A, Bruyns E, Korinek V, Angelisova P, et al. Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation. J Exp Med. 2000;191:1591-604 pubmed
    ..tyrosine-phosphorylated protein and binds the major negative regulator of Src kinases, the tyrosine kinase Csk. After activation of peripheral blood alpha/beta T cells, PAG becomes rapidly dephosphorylated and dissociates from ..
  27. Lee N, Cheng C. Protein kinases and adherens junction dynamics in the seminiferous epithelium of the rat testis. J Cell Physiol. 2005;202:344-60 pubmed
    ..c-Src (the cellular form of the v-src transforming gene of Rous Sarcoma virus, RSV), carboxyl-terminal Src kinase (Csk), and casein kinase 2 (CK2), during AJ assembly...