p38 Mitogen-Activated Protein Kinase (p38 MAPK)

p38 mitogen-activated protein kinases (MAPKs) are a class of serine/threonine protein kinases that play a central role in cellular responses to stress and inflammation. They are activated by various extracellular stimuli, including cytokines, ultraviolet irradiation, heat shock, osmotic shock, oxidative stress, and growth factors. The p38 MAPK pathway is evolutionarily conserved and is involved in regulating cell differentiation, apoptosis, autophagy, and inflammatory responses. There are four main isoforms: p38α (MAPK14), p38β (MAPK11), p38γ (MAPK12/ERK6), and p38δ (MAPK13/SAPK4). Activation typically follows a three-tiered kinase cascade: MAPKKKs activate MKKs, which phosphorylate p38 isoforms on a TGY motif. Activated p38 MAPKs phosphorylate numerous substrates, regulating inflammation, cell cycle arrest, and apoptosis. Given their role in inflammation, components of the p38 pathway are considered potential therapeutic targets for autoimmune diseases, chronic inflammatory conditions, neurodegenerative disorders, and cancer.

Other names

MAPK14MAPK11MAPK12MAPK13SAPK4ERK6

ATP-competitive inhibition (for small molecule inhibitors); Dephosphorylation by phosphatases (endogenous regulation)