Mitogen-activated protein kinase 14 (p38α) and Mitogen-activated protein kinase 11 (p38β) (p38α (MAPK14), p38β (MAPK11))

Mitogen-activated protein kinase 14 (p38α) and mitogen-activated protein kinase 11 (p38β) are serine/threonine protein kinases in the mitogen-activated protein kinase family, primarily involved in cellular responses to stress stimuli such as cytokines, UV irradiation, heat shock, and osmotic stress[6][7]. Activated through dual phosphorylation by upstream MAPK kinases (notably MKK3/6), they play central roles in regulating inflammation, cell cycle checkpoints, apoptosis, differentiation, and post-transcriptional gene regulation[1][2][3][4][5][6][7]. They are therapeutic targets for a range of inflammatory and autoimmune diseases, as well as cancer. Several experimental and clinical drugs target the p38 MAPK pathway by inhibiting kinase activity, though toxicity and limited efficacy have so far challenged clinical development[3][4][6].

Other names

p38 MAP kinase alpha (p38α)p38 MAP kinase beta (p38β)MAPK14 (p38α)MAPK11 (p38β)CSBP (Cytokinin Specific Binding Protein, p38α)RK (alternative name for p38α)SAPK2a (p38α)SAPK2b (p38β)Stress-activated protein kinase 2 (alternative, less specific)p38 MAPKs (family, used collectively for α and β, as well as γ and δ)

Direct inhibition of kinase activity (ATP-competitive inhibitors bind to the ATP pocket and prevent phosphorylation of substrates); Inhibition of phosphorylation of downstream targets (e.g., MAPKAP kinase 2, transcription factors like ATF2, p53); Suppression of cytokine production or cellular stress pathways