Cdc2-like kinase (CLK)

Cdc2-like kinase (CLK) refers to a family of dual-specificity protein kinases (CLK1–4) classified within the CMGC kinase superfamily, capable of phosphorylating both serine/threonine and tyrosine residues[1][4]. CLKs are central regulators of alternative mRNA splicing, primarily through the phosphorylation of serine/arginine-rich (SR) splicing factors (SRSF1-12), affecting spliceosome assembly, transcript diversity, and gene expression[1][4][7]. Dysregulation of CLK activity and consequent aberrant splicing are implicated in the pathogenesis of various diseases, including cancer, neurodegenerative diseases, muscular dystrophy, viral infections, and inflammatory disorders[4]. CLKs are validated therapeutic targets, and several small-molecule inhibitors—such as TG003, CX-4945, and Lorecivivint—are under investigation in preclinical and clinical studies for the treatment of splicing-related disorders and tumors[1][2][4]. Their essential regulatory roles in cellular processes, along with links to multiple disease pathways, highlight their significance in biomedical research and drug development.

Other names

LAMMER kinaseCDC-like kinaseDual specificity protein kinase CLKSR protein kinase

Inhibition of kinase activity (direct inhibition of ATP-binding site); Modulation of alternative splicing by blocking phosphorylation of SR proteins; Regulation of cell cycle and survival signaling pathways