Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

CSK-Homologous Kinase

  • Heung-Chin Cheng
  • Gahana Advani
  • Mohammed Iqbal Hossain
  • Nadia L. Y. Ng
  • Ya Chee Lim
  • Anderly C. Chüeh
  • Mohd Aizuddin Kamaruddin
  • Yuh-Ping Chong
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_185

Synonyms

Historical Background

C-terminal Src kinase (Csk) and Csk-homologous kinase (also referred to as Csk-type kinase, Ctk) are the endogenous inhibitors of Src-family kinases (SFKs). Both inhibitors inactivate SFKs by phosphorylating their consensus C-terminal inhibitory tyrosine (corresponds to Tyr-527 in c-Src) that stabilizes the inactive SFK conformation (Fig. 1). The discovery of Csk can be traced back to an important study performed two decades ago (Okada and Nakagawa 1989). The study showed that Tyr-527 of c-Src did not undergo autophosphorylation. Rather, it was phosphorylated by a putative upstream tyrosine kinase that was originally termed neonatal brain type of protein tyrosine kinase (N-PTK) isolated from the membrane fraction...
This is a preview of subscription content, log in to check access.

References

  1. Advani G, Chueh AC, Lim YC, Dhillon A, Cheng H-C. Csk-homologous kinase (Chk/Matk): a molecular policeman suppressing cancer formation and progression. Front Biol. 2015;10:195–202.Google Scholar
  2. Avraham S, Jiang S, Ota S, Fu Y, Deng B, Dowler LL, White RA, Avraham H. Structural and functional studies of the intracellular tyrosine kinase MATK gene and its translated product. J Biol Chem. 1995;270:1833–42.PubMedGoogle Scholar
  3. Ayrapetov MK, Nam NH, Ye G, Kumar A, Parang K, Sun G. Functional diversity of Csk, Chk, and Src SH2 domains due to a single residue variation. J Biol Chem. 2005;280:25780–7.PubMedGoogle Scholar
  4. Bennett BD, Cowley S, Jiang S, London R, Deng B, Grabarek J, Groopman JE, Goeddel DV, Avraham H. Identification and characterization of a novel tyrosine kinase from megakaryocytes. J Biol Chem. 1994;269:1068–74.PubMedPubMedCentralGoogle Scholar
  5. Chan KC, Lio DS, Dobson RCJ, Jarasrassamee B, Hossain MI, Roslee AK, Ia KK, Perugini MA, Cheng H-C. Development of the procedures for high yield expression and rapid purification of active recombinant Csk-homologous kinase (CHK) – comparison of the catalytic activities of CHK and CSK. Protein Expr Purif. 2010;74:139–47.PubMedGoogle Scholar
  6. Chen Y, Tan SY, Petersson BF, Khor YM, Gopalakrishnan SK, Tan D. Occult recurrence of monomorphic epitheliotropic intestinal T-cell lymphoma and the role of MATK gene expression in diagnosis. Hematol Oncol. 2016.  https://doi.org/10.1002/hon.2288.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Cheng H-C, Chong YP, Ia KK, Tan O, Mulhern TD. Csk homologous kinase. UCSD-Nature Molecule Pages. 2006.  https://doi.org/10.1038/mp.a000705.01.CrossRefGoogle Scholar
  8. Chong YP, Mulhern TD, Zhu HJ, Fujita DJ, Bjorge JD, Tantiongco JP, Sotirellis N, Lio DS, Scholz G, Cheng HC. A novel non-catalytic mechanism employed by the C-terminal Src-homologous kinase to inhibit Src-family kinase activity. J Biol Chem. 2004;279:20752–66.PubMedGoogle Scholar
  9. Chong YP, Ia KK, Mulhern TD, Cheng HC. Endogenous and synthetic inhibitors of the Src-family protein tyrosine kinases. Biochim Biophys Acta. 2005a;1754:210–20.PubMedGoogle Scholar
  10. Chong YP, Mulhern TD, Cheng HC. C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK)--endogenous negative regulators of Src-family protein kinases. Growth Factors. 2005b;23:233–44.PubMedGoogle Scholar
  11. Chong YP, Chan AS, Chan KC, Williamson NA, Lerner EC, Smithgall TE, Bjorge JD, Fujita DJ, Purcell AW, Scholz G, Mulhern TD, Cheng HC. C-terminal Src kinase-homologous kinase (CHK), a unique inhibitor inactivating multiple active conformations of Src family tyrosine kinases. J Biol Chem. 2006;281:32988–99.PubMedGoogle Scholar
  12. Chow LM, Davidson D, Fournel M, Gosselin P, Lemieux S, Lyu MS, Kozak CA, Matis LA, Veillette A. Two distinct protein isoforms are encoded by ntk, a csk-related tyrosine protein kinase gene. Oncogene. 1994;9:3437–48.PubMedPubMedCentralGoogle Scholar
  13. Dokmanovic M, Wu Y, Shen Y, Chen J, Hirsch DS, Wu WJ. Trastuzumab-induced recruitment of Csk-homologous kinase (CHK) to ErbB2 receptor is associated with ErbB2-Y1248 phosphorylation and ErbB2 degradation to mediate cell growth inhibition. Cancer Biol Ther. 2014;15:1029–41.PubMedPubMedCentralGoogle Scholar
  14. Gunn NJ, Gorman MA, Dobson RC, Parker MW, Mulhern TD. Purification, crystallization, small-angle X-ray scattering and preliminary X-ray diffraction analysis of the SH2 domain of the Csk-homologous kinase. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011;67:336–9.PubMedPubMedCentralGoogle Scholar
  15. Hamaguchi I, Yamaguchi N, Suda J, Iwama A, Hirao A, Hashiyama M, Aizawa S, Suda T. Analysis of CSK homologous kinase (CHK/HYL) in hematopoiesis by utilizing gene knockout mice. Biochem Biophys Res Commun. 1996;224:172–9.PubMedGoogle Scholar
  16. Hinoue T, Weisenberger DJ, Lange CP, Shen H, Byun HM, Van Den Berg D, Malik S, Pan F, Noushmehr H, van Dijk CM, Tollenaar RA, Laird PW. Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome Res. 2012;22:271–82.PubMedPubMedCentralGoogle Scholar
  17. Huang H, Li L, Wu C, Schibli D, Colwill K, Ma S, Li C, Roy P, Ho K, Songyang Z, Pawson T, Gao Y, Li SS. Defining the specificity space of the human SRC homology 2 domain. Mol Cell Proteomics. 2008;7:768–84.PubMedPubMedCentralGoogle Scholar
  18. Huang K, Wang YH, Brown A, Sun G. Identification of N-terminal lobe motifs that determine the kinase activity of the catalytic domains and regulatory strategies of Src and Csk protein tyrosine kinases. J Mol Biol. 2009;386:1066–77.PubMedPubMedCentralGoogle Scholar
  19. Ia KK, Mills RD, Hossain MI, Chan K-C, Jarasrassamee B, Jorissen RN, Cheng H-C. Structural elements and allosteric mechanisms governing regulation and catalysis of Csk-family kinases and their inhibition of Src-family kinases. Growth Factors. 2010;28:329–50.PubMedGoogle Scholar
  20. Ia KK, Jeschke GR, Deng Y, Kamaruddin MA, Williamson NA, Scanlon DB, Culvenor JG, Hossain MI, Purcell AW, Liu S, Zhu HJ, Catimel B, Turk BE, Cheng HC. Defining the substrate specificity determinants recognized by the active site of C-terminal Src kinase-homologous kinase (CHK) and identification of beta-synuclein as a potential CHK physiological substrate. Biochemistry. 2011;50:6667–77.PubMedPubMedCentralGoogle Scholar
  21. Kim S, Zagozdzon R, Meisler A, Baleja JD, Fu Y, Avraham S, Avraham H. Csk homologous kinase (CHK) and ErbB-2 interactions are directly coupled with CHK negative growth regulatory function in breast cancer. J Biol Chem. 2002;277:36465–70.PubMedGoogle Scholar
  22. Kim SO, Avraham S, Jiang S, Zagozdzon R, Fu Y, Avraham HK. Differential expression of Csk homologous kinase (CHK) in normal brain and brain tumors. Cancer. 2004;101:1018–27.PubMedGoogle Scholar
  23. Kuo SS, Moran P, Gripp J, Armanini M, Phillips HS, Goddard A, Caras IW. Identification and characterization of Batk, a predominantly brain-specific non-receptor protein tyrosine kinase related to Csk. J Neurosci Res. 1994;38:705–15.PubMedGoogle Scholar
  24. Kuo SS, Armanini MP, Phillips HS, Caras IW. Csk and BatK show opposite temporal expression in the rat CNS: consistent with its late expression in development, BatK induces differentiation of PC12 cells. Eur J Neurosci. 1997;9:2383–93.PubMedGoogle Scholar
  25. Laffaire J, Everhard S, Idbaih A, Criniere E, Marie Y, de Reynies A, Schiappa R, Mokhtari K, Hoang-Xuan K, Sanson M, Delattre JY, Thillet J, Ducray F. Methylation profiling identifies 2 groups of gliomas according to their tumorigenesis. Neuro-Oncology. 2011;13:84–98.PubMedGoogle Scholar
  26. Lamers MB, Antson AA, Hubbard RE, Scott RK, Williams DH. Structure of the protein tyrosine kinase domain of C-terminal Src kinase (CSK) in complex with staurosporine. J Mol Biol. 1999;285:713–25.PubMedGoogle Scholar
  27. Lee BC, Avraham S, Imamoto A, Avraham HK. Identification of the nonreceptor tyrosine kinase MATK/CHK as an essential regulator of immune cells using Matk/CHK-deficient mice. Blood. 2006;108:904–7.PubMedPubMedCentralGoogle Scholar
  28. Levinson NM, Seeliger MA, Cole PA, Kuriyan J. Structural basis for the recognition of c-Src by its inactivator Csk. Cell. 2008;134:124–34.PubMedPubMedCentralGoogle Scholar
  29. Levinson NM, Visperas PR, Kuriyan J. The tyrosine kinase Csk dimerizes through its SH3 domain. PLoS One. 2009;4:e7683.PubMedPubMedCentralGoogle Scholar
  30. Lin X, Ayrapetov MK, Lee S, Parang K, Sun G. Probing the communication between the regulatory and catalytic domains of a protein tyrosine kinase, Csk. Biochemistry. 2005;44:1561–7.PubMedGoogle Scholar
  31. Mitsuhashi H, Futai E, Sasagawa N, Hayashi Y, Nishino I, Ishiura S. Csk-homologous kinase interacts with SHPS-1 and enhances neurite outgrowth of PC12 cells. J Neurochem. 2008;105:101–12.PubMedGoogle Scholar
  32. Nada S, Okada M, MacAuley A, Cooper JA, 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.PubMedGoogle Scholar
  33. Nakayama Y, Kawana A, Igarashi A, Yamaguchi N. Involvement of the N-terminal unique domain of Chk tyrosine kinase in Chk-induced tyrosine phosphorylation in the nucleus. Exp Cell Res. 2006;312:2252–63.PubMedGoogle Scholar
  34. O’Hare T, Eide CA, Deininger MW. Persistent LYN signaling in imatinib-resistant, BCR-ABL-independent chronic myelogenous leukemia. J Natl Cancer Inst. 2008;100:908–9.PubMedGoogle Scholar
  35. Ogawa A, Takayama Y, Sakai H, Chong KT, Takeuchi S, Nakagawa A, Nada S, Okada M, Tsukihara T. Structure of the carboxyl-terminal Src kinase, Csk. J Biol Chem. 2002;277:14351–4.PubMedGoogle Scholar
  36. Okada M, Nakagawa H. A protein tyrosine kinase involved in regulation of pp60c-src function. J Biol Chem. 1989;264:20886–93.PubMedPubMedCentralGoogle Scholar
  37. Radhakrishnan Y, Shen X, Maile LA, Xi G, Clemmons DR. IGF-I stimulates cooperative interaction between the IGF-I receptor and CSK homologous kinase that regulates SHPS-1 phosphorylation in vascular smooth muscle cells. Mol Endocrinol. 2011;25:1636–49.PubMedPubMedCentralGoogle Scholar
  38. Samokhvalov I, Hendrikx J, Visser J, Belyavsky A, Sotiropolous D, Gu H. Mice lacking a functional chk gene have no apparent defects in the hematopoietic system. Biochem Mol Biol Int. 1997;43:115–22.PubMedPubMedCentralGoogle Scholar
  39. Seong J, Lu S, Ouyang M, Huang H, Zhang J, Frame MC, Wang Y. Visualization of Src activity at different compartments of the plasma membrane by FRET imaging. Chem Biol. 2009;16:48–57.PubMedPubMedCentralGoogle Scholar
  40. Shen X, Xi G, Radhakrishnan Y, Clemmons DR. Identification of novel SHPS-1-associated proteins and their roles in regulation of insulin-like growth factor-dependent responses in vascular smooth muscle cells. Mol Cell Proteomics. 2009;8:1539–51.PubMedPubMedCentralGoogle Scholar
  41. Tan SY, Ooi AS, Ang MK, Koh M, Wong JC, Dykema K, Ngeow J, Loong S, Gatter K, Tan L, Lim LC, Furge K, Tao M, Lim ST, Loong F, Cheah PL, Teh BT. Nuclear expression of MATK is a novel marker of type II enteropathy-associated T-cell lymphoma. Leukemia. 2011;25:555–7.PubMedGoogle Scholar
  42. Tan SY, Chuang SS, Tang T, Tan L, Ko YH, Chuah KL, Ng SB, Chng WJ, Gatter K, Loong F, Liu YH, Hosking P, Cheah PL, Teh BT, Tay K, Koh M, Lim ST. Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8alphaalpha phenotype. Leukemia. 2013;27:1688–96.PubMedGoogle Scholar
  43. Wong L, Lieser S, Chie-Leon B, Miyashita O, Aubol B, Shaffer J, Onuchic JN, Jennings PA, Woods Jr VL, Adams JA. Dynamic coupling between the SH2 domain and active site of the COOH terminal Src kinase, Csk. J Mol Biol. 2004;341:93–106.PubMedGoogle Scholar
  44. Wong L, Lieser SA, Miyashita O, Miller M, Tasken K, Onuchic JN, Adams JA, Woods Jr VL, Jennings PA. Coupled motions in the SH2 and kinase domains of Csk control Src phosphorylation. J Mol Biol. 2005;351:131–43.PubMedGoogle Scholar
  45. Yamaguchi N, Nakayama Y, Urakami T, Suzuki S, Nakamura T, Suda T, Oku N. Overexpression of the Csk homologous kinase (Chk tyrosine kinase) induces multinucleation: a possible role for chromosome-associated Chk in chromosome dynamics. J Cell Sci. 2001;114:1631–41.PubMedPubMedCentralGoogle Scholar
  46. Zagozdzon R, Kaminski R, Fu Y, Fu W, Bougeret C, Avraham HK. Csk homologous kinase (CHK), unlike Csk, enhances MAPK activation via Ras-mediated signaling in a Src-independent manner. Cell Signal. 2006;18:871–81.PubMedGoogle Scholar
  47. Zhu S, Bjorge JD, Cheng HC, Fujita DJ. Decreased CHK protein levels are associated with Src activation in colon cancer cells. Oncogene. 2008;27:2027–34.PubMedGoogle Scholar
  48. Zrihan-Licht S, Lim J, Keydar I, Sliwkowski MX, Groopman JE, Avraham H. Association of csk-homologous kinase (CHK) (formerly MATK) with HER-2/ErbB-2 in breast cancer cells. J Biol Chem. 1997;272:1856–63.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Heung-Chin Cheng
    • 1
  • Gahana Advani
    • 1
  • Mohammed Iqbal Hossain
    • 1
  • Nadia L. Y. Ng
    • 1
  • Ya Chee Lim
    • 1
    • 2
  • Anderly C. Chüeh
    • 3
  • Mohd Aizuddin Kamaruddin
    • 1
  • Yuh-Ping Chong
    • 4
  1. 1.Cell Signaling Research Laboratories, Department of Biochemistry and Molecular BiologyBio21 Molecular Science and Biotechnology Institute, University of MelbourneParkvilleAustralia
  2. 2.PAP Rashidah Sa’adatul Bolkiah Institute of Health SciencesUniversiti Brunei DarussalamGadongBrunei Darussalam
  3. 3.Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical ResearchParkvilleAustralia
  4. 4.Edinburgh Cancer Research CentreWestern General HospitalEdinburghUK