Dual specificity protein kinase CLK4 (CLK4)

Dual specificity protein kinase CLK4 is a serine/threonine and tyrosine kinase belonging to the CDC2-like kinase family, specifically the CMGC kinase group, often called the LAMMER kinases due to a conserved motif[1][3][4]. CLK4 phosphorylates serine- and arginine-rich domain (SR) proteins, influencing spliceosome assembly and alternative pre-mRNA splicing[1][4]. It is implicated in a network of gene expression regulatory mechanisms, and recent studies have highlighted CLK4 as a critical regulator of cardiac hypertrophy by phosphorylating nexilin (NEXN) to maintain healthy sarcomere structure and cardiac function[2]. Genetic deficiency or inhibition of CLK4 can lead to pathological alterations in the heart, including hypertrophy and failure. CLK4 is under investigation as a potential therapeutic target, especially in conditions where alternative splicing or cardiac function is disrupted, although selective, clinically approved drugs for this kinase are not currently available[7].

Other names

CDC like kinase 4CDC-like kinase 4Cdc2-like kinase 4protein serine/threonine kinase Clk4dual specificity protein kinase CLK4LAMMER protein kinaseCLK family member 4

Inhibition of CLK4 prevents phosphorylation of SR proteins, resulting in modulation of splicing patterns. Small molecule kinase inhibitors bind the ATP-binding pocket of CLK4, disrupting its catalytic activity.