CDC-like kinase 2 (CLK2) (CLK2)

CDC-like kinase 2 (CLK2) is a dual-specificity kinase that plays a central role in the regulation of pre-mRNA splicing by phosphorylating serine/arginine-rich (SR) proteins (UniProt P49760). This phosphorylation facilitates the assembly of the spliceosome and influences the selection of alternative splice sites, thereby diversifying the proteome (PubMed: 28244870). Beyond splicing, CLK2 is involved in critical cellular processes such as the DNA damage response, cell cycle progression, and metabolic regulation, specifically hepatic gluconeogenesis (PubMed: 21706013). In the context of disease, CLK2 is often upregulated in various malignancies, including breast, lung, and colorectal cancers, where it promotes oncogenic splicing variants that drive tumor growth and survival (PubMed: 30305517). Therapeutic strategies targeting CLK2 involve small-molecule inhibitors, such as TG003 and T-025, which aim to correct aberrant splicing patterns in cancer cells (PubMed: 29155427). However, because CLK2 regulates fundamental biological processes, potential safety concerns include systemic toxicity and unintended effects on metabolic homeostasis.

Other names

Dual specificity protein kinase CLK2Cdc2-like kinase 2CLK2

Small molecule inhibition of the kinase domain to prevent phosphorylation of serine/arginine-rich (SR) proteins, thereby modulating alternative splicing of pre-mRNAs.