CDC-like kinase (CLK) (CLK)

CDC-like kinases (CLK1-4) are a family of four dual-specificity protein kinases—CLK1, CLK2, CLK3, and CLK4—that are essential regulators of pre-mRNA splicing [1.1.5, 1.2.2]. They function by phosphorylating serine/arginine-rich (SR) proteins, which are critical components of the spliceosome machinery [1.2.1, 1.3.1]. By modulating the phosphorylation state of these SR proteins, CLKs influence the selection of splice sites and the production of diverse protein isoforms from a single gene [1.2.1, 1.4.2]. Dysregulation of CLK activity and the resulting aberrant splicing are implicated in a wide range of diseases, including various cancers (such as triple-negative breast cancer), neurodegenerative disorders like Alzheimer's disease, and viral infections such as influenza and HIV [1.1.5, 1.2.4, 1.4.3]. Consequently, CLKs have emerged as promising therapeutic targets, with several small-molecule inhibitors currently in clinical and preclinical development [1.2.2, 1.4.3]. These inhibitors typically target the ATP-binding pocket of the kinases to modulate the splicing landscape, offering a unique mechanism for treating complex diseases at the molecular level [1.2.1, 1.4.1].

Other names

CLK1CLK2CLK3CLK4STYLAMMER kinaseCDC2-like kinaseDual specificity protein kinase CLK

Inhibition of the ATP-binding pocket of CLK kinases, preventing phosphorylation of SR proteins and modulating pre-mRNA splicing.