SRPK

Serine/arginine protein kinases, abbreviated SRPKs, are a family of serine/threonine kinases that specifically phosphorylate the RS domains of serine/arginine-rich (SR) splicing factors. In vertebrates the family includes SRPK1, SRPK2, and SRPK3, while other lineages may contain a single SRPK gene. SRPKs are key regulators of mRNA splicing through their influence on SR protein activity.

SRPKs are characterized by a distinctive architecture that includes two consecutive catalytic kinase domains (KD1 and KD2) within a single polypeptide, along with regulatory regions that influence subcellular localization and substrate interaction. This double-kinase arrangement is conserved across the family and underpins their unique substrate recognition of RS domains.

Functionally, SRPKs phosphorylate the RS domains of SR proteins such as SRSF1 and related family members. This phosphorylation modulates SR protein interactions with other splicing factors and transport receptors, thereby influencing the assembly and dynamics of the spliceosome and the regulation of alternative splicing. Through these effects, SRPK activity impacts gene expression programs and can affect processes such as development and cellular differentiation.

Localization and regulation of SRPK activity are tissue- and context-dependent. While predominantly cytoplasmic, SRPKs affect the nuclear availability and activity of SR proteins, linking cellular signaling to splicing outcomes. SRPKs are regulated by cellular signaling pathways and protein–protein interactions; their activity can be probed with selective inhibitors in experimental and therapeutic contexts.

In research and medicine, altered SRPK function has been associated with diseases including cancer and neurodegenerative conditions. SRPK inhibitors are studied as tools to dissect splicing regulation and as potential therapeutic agents, including exploration for antiviral strategies due to SR protein involvement in viral gene expression.