Mitogen- and stress-activated protein kinase (MSK) (MSK)

Mitogen- and stress-activated protein kinases (MSKs), comprising the isoforms MSK1 and MSK2, are nuclear serine/threonine kinases belonging to the AGC kinase family (UniProt O75582, O75676). They are activated by the extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathways in response to growth factors, cytokines, and cellular stress (Arthur, 2008, FEBS Letters). MSKs play a critical role in the nucleosomal response by phosphorylating histone H3 at Ser10 and Ser28, which facilitates chromatin remodeling and the rapid induction of immediate-early genes (Soloaga et al., 2003, EMBO Journal). Additionally, they regulate gene transcription by phosphorylating transcription factors such as CREB and ATF1, which is essential for the production of the anti-inflammatory cytokine interleukin-10 (IL-10) (Reber et al., 2017, Frontiers in Immunology). Due to their role in balancing pro- and anti-inflammatory signals, MSKs are considered potential therapeutic targets for chronic inflammatory diseases like psoriasis and asthma, as well as certain cancers where they contribute to cell survival (Naqvi et al., 2012, Biochem J). While no MSK-specific inhibitors are currently approved for clinical use, tool compounds like SB-747651A are extensively used in research to validate MSKs as druggable targets (PubChem CID 16219501).

Other names

RPS6KA5RPS6KA4Ribosomal protein S6 kinase alpha-5Ribosomal protein S6 kinase alpha-4RSKLMSK1MSK2

Inhibition of kinase activity through ATP-competitive binding