p38 mitogen-activated protein kinase alpha (MAPK14) and p38 mitogen-activated protein kinase beta (MAPK11) (p38α (for MAPK14), p38β (for MAPK11))

p38 mitogen-activated protein kinases α and β are stress-responsive serine/threonine kinases of the MAP kinase family, encoded in humans by the MAPK14 (p38α) and MAPK11 (p38β) genes[7][8][10]. These kinases function as key signal transducers in response to inflammatory cytokines, environmental stresses (such as heat shock and UV irradiation), and other external stimuli. p38α is the predominant isoform in immune cells and is critical for the production of inflammatory cytokines including TNFα and IL-6, while p38β expression is highest in endothelial cells but generally lower than p38α in most immune lineages[4][8]. p38 MAPKs regulate numerous cellular processes including gene expression, apoptosis, cell cycle, senescence, cell differentiation, and metabolic adaptation. They are central in the pathogenesis of inflammatory diseases and several cancers, and they are validated drug targets in both preclinical and clinical settings[3][6][7][10]. Selective inhibitors of p38α/β have been developed and tested in inflammatory, cardiovascular, and some oncological indications. The broad roles of p38 kinases, however, pose safety challenges, particularly concerning immunosuppression and inhibition of essential stress responses.

Other names

SAPK2a (for p38α)p38 MAPK alphaSAPK2b (for p38β)p38 MAPK betaRK (for p38 MAPK)CSBP (Cytokinin Specific Binding Protein)Stress-activated protein kinase 2 (SAPK2)

Inhibition of kinase activity by competitive binding at the ATP site Blockade of downstream phosphorylation of transcription factors and other substrates Suppression of inflammatory cytokine production