Cdc2-like kinase 1, 2, 3, and 4 (CLK1, CLK2, CLK3, CLK4)

Cdc2-like kinases (CLK1, CLK2, CLK3, and CLK4) are a family of dual-specificity protein kinases characterized by the conserved LAMMER motif. Their primary function is the phosphorylation of serine/arginine-rich domains on splicing factors, regulating pre-mRNA alternative splicing in the nucleus. These kinases thereby influence the production of multiple mRNA isoforms from a single gene, impacting cell growth, survival, and differentiation. CLKs are evolutionarily conserved and found to be dysregulated in various cancers. Pharmacological inhibition of CLKs is being explored as a means of correcting mis-splicing in disease, but developing selective and safe drugs remains challenging due to the broad biological roles of these enzymes.

Other names

CLK kinasesLAMMER kinasesDual specificity protein kinase CLK1, CLK2, CLK3, CLK4Neuronal cdc2-like kinase (specifically for nCLK)

Drugs typically function as small-molecule inhibitors that bind to the ATP-binding site of CLKs, inhibiting kinase activity and thus altering SR protein phosphorylation and splicing regulation.