Journal article

Csk-homologous kinase (Chk) is an efficient inhibitor of Src-family kinases but a poor catalyst of phosphorylation of their C-terminal regulatory tyrosine

Gahana Advani, Ya Chee Lim, Bruno Catimel, Daisy Sio Seng Lio, Nadia LY Ng, Anderly C Chueh, Mai Tran, Mohd Ishtiaq Anasir, Heather Verkade, Hong-Jian Zhu, Benjamin E Turk, Thomas E Smithgall, Ching-Seng Ang, Michael Griffin, Heung-Chin Cheng

CELL COMMUNICATION AND SIGNALING | BIOMED CENTRAL LTD | Published : 2017

Abstract

BACKGROUND: C-terminal Src kinase (Csk) and Csk-homologous kinase (Chk) are the major endogenous inhibitors of Src-family kinases (SFKs). They employ two mechanisms to inhibit SFKs. First, they phosphorylate the C-terminal tail tyrosine which stabilizes SFKs in a closed inactive conformation by engaging the SH2 domain in cis. Second, they employ a non-catalytic inhibitory mechanism involving direct binding of Csk and Chk to the active forms of SFKs that is independent of phosphorylation of their C-terminal tail. Csk and Chk are co-expressed in many cell types. Contributions of the two mechanisms towards the inhibitory activity of Csk and Chk are not fully clear. Furthermore, the determinants..

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Grants

Awarded by NHMRC Australia


Awarded by NIH


Awarded by Australian Research Council Future Fellowship


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Funding Acknowledgements

Work described in this manuscript was supported by funds from NHMRC Australia (1050486) (to H.-C.C), NIH R01 AI102724 (to T.E.S.) and NIH RO1 (GM104047) (to B. T.). M.G is the recipient of an Australian Research Council Future Fellowship (project number FT140100544).