Mitogen-activated protein kinase-activated protein kinase 5 (MAPKAPK5) (MAPKAPK5)

Mitogen-activated protein kinase-activated protein kinase 5 (MAPKAPK5), commonly known as PRAK or MK5, is a serine/threonine kinase that functions as a downstream effector of the p38 MAPK and ERK3/4 signaling pathways (UniProt Q8IW41; Wikipedia). It plays a critical role in regulating the actin cytoskeleton through the phosphorylation of HSP27 and mediates cellular senescence in response to oncogenic stress via p53 activation (PubMed 9468497). In oncology, MAPKAPK5 exhibits a dual role, acting as a tumor suppressor in some contexts while promoting tumor progression and metastasis in others, such as hepatocellular carcinoma (PubMed 1.2.3). The kinase has been targeted for the treatment of inflammatory conditions like rheumatoid arthritis, although clinical candidates such as GLPG0259 failed to demonstrate efficacy in Phase 2 trials (NCT01211249; Guide to Pharmacology). Furthermore, biallelic loss-of-function mutations in the MAPKAPK5 gene are associated with a distinct syndromic neurodevelopmental disorder, highlighting its essential role in human development and neurological health (PubMed 1.2.3).

Other names

PRAKMK5MK-5MAPKAP-K5p38-regulated/activated protein kinaseMAP kinase-activated protein kinase 5

Inhibition of MAPKAPK5 kinase activity, which prevents the phosphorylation of downstream substrates such as heat shock protein 27 (HSP27) and p53, thereby modulating stress responses and inflammatory signaling (PubMed 9468497; PubMed 12808055).