Mitogen-activated protein kinase 11 (MAPK11) (MAPK11)

Mitogen-activated protein kinase 11 (MAPK11), also known as p38 MAPK beta, is a serine/threonine kinase that belongs to the p38 mitogen-activated protein kinase family [4, 11]. It plays a central role in the cellular response to environmental stressors, such as oxidative stress and UV radiation, as well as pro-inflammatory cytokines like TNF-alpha and IL-1 beta [1, 18]. Upon activation by upstream kinases like MKK3 and MKK6, p38 beta phosphorylates various downstream targets, including transcription factors and other kinases, to regulate processes such as gene expression, mRNA stability, and cell cycle progression [3, 8, 19]. While it shares significant functional redundancy with the more abundant p38 alpha isoform, p38 beta is particularly prominent in the brain and heart [11, 16]. In clinical contexts, it is a major target for treating chronic inflammatory diseases and certain cancers, such as Sézary syndrome, where its dysregulation contributes to disease pathogenesis [6, 11]. However, the development of p38 beta inhibitors has faced significant hurdles due to off-target effects and safety concerns, particularly hepatotoxicity and skin rashes, which have limited their success in clinical trials [7, 10, 16].

Other names

p38-betap38bSAPK2BSAPK2bp38-2PRKM11

Inhibition of p38 MAPK kinase activity [1, 3, 10]