Structural elements and allosteric mechanisms governing regulation and catalysis of CSK-family kinases and their inhibition of Src-family kinases

Kim K. Ia, Ryan D. Mills, Mohammed I. Hossain, Khai Chew Chan, Boonyarin Jarasrassamee, Robert N. Jorissen, Heung Chin Cheng

Research output: Contribution to journalReview articlepeer-review

19 Citations (Scopus)


C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are endogenous inhibitors constraining the activity of the oncogenic Src-family kinases (SFKs) in cells. Both kinases suppress SFKs by selectively phosphorylating their consensus C-terminal regulatory tyrosine. In addition to phosphorylation, CHK can suppress SFKs by a unique non-catalytic inhibitory mechanism that involves tight binding of CHK to SFKs to form stable complexes. In this review, we discuss how allosteric regulators, phosphorylation, and inter-domain interactions interplay to govern the activity of CSK and CHK and their ability to inhibit SFKs. In particular, based upon the published results of structural and biochemical analysis of CSK and CHK, we attempt to chart the allosteric networks in CSK and CHK that govern their catalysis and ability to inhibit SFKs. We also discuss how the published three-dimensional structure of CSK complexed with an SFK member sheds light on the structural basis of substrate recognition by protein kinases.

Original languageEnglish
Pages (from-to)329-350
JournalGrowth Factors
Issue number5
Publication statusPublished - 1 Oct 2010
Externally publishedYes


  • Allosteric regulation
  • CHK
  • CSK
  • Catalysis
  • Protein kinase
  • Src-family kinases

ASJC Scopus subject areas

  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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