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 β-synuclein, α-tubulin, α-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

The drug–target association network (D–T network) for BZ.

<p>Green, the five compounds from BZ; Pink, the target-associated genes; Yellow, the shared genes among the five compounds.</p

Contents of 15 constituents in 7 decoctions.

<p>Contents of 15 constituents in 7 decoctions.</p

The drug–herb interaction network (D–H network) for BZ.

<p>BS, <i>P. corylifolia</i> and <i>C. monnieri</i>; BW, <i>P. corylifolia</i> and <i>A. carmichaelii</i>; BWS, <i>P. corylifolia</i>, <i>C. monnieri</i> and <i>A. carmichaelii</i>.</p

LC-MS/MS method validation for 15 constituents from BZ.

<p>LC-MS/MS method validation for 15 constituents from BZ.</p

Plasma concentration-time curves for psoralen, isopsoralen, psoralidin, xanthotoxin, and bergapten in SD rats after single oral administration of BZ.

<p>Plasma concentration-time curves for psoralen, isopsoralen, psoralidin, xanthotoxin, and bergapten in SD rats after single oral administration of BZ.</p