Regulation, targets and functions of CHK

Src family kinases (SFKs) play pivotal roles in multiple signaling pathways (Yeatman, 2004). SFK activity is inhibited by phosphorylation at its C-terminal tyrosine, by CSK (C-terminal Src kinase) and CHK (CSK-homologous kinase). CHK expression is restricted to normal hematopoietic cells, brain, and colon tissues. Downregulation of CHK in brain and colon tumors contributes to tumorigenicity in these tissues. CHK does not phosphorylate Src efficiently, however, in contrast to CSK, CHK inhibits Src kinase activity allosterically. Although the functions of CHK are still largely unknown, potential substrates of CHK including beta-synuclein, alpha-tubulin, alpha-spectrin, 14-3-3, and Hsp90 have been identified. CHK is regulated epigenetically via promoter methylation. As the unknown roles of CHK are beginning to be revealed, current knowledge of regulation, molecular targets and functions of CHK is summarized, and important topics for future CHK research are discussed.

Automated summary

This article summarizes the important roles of Src family kinases (SFKs) in multiple signaling pathways, with a focus on the inhibitory function of CHK in tumor development and its regulation of various substrates. Although the precise functions of CHK are still unclear, it has been found to allosterically inhibit Src kinase activity and is regulated through promoter methylation.