p38 MAPK Signaling Pathway

p38 MAPKs (Mitogen-Activated Protein Kinases) are members of mammalian stress-activated MAPK family. The p38 MAPK subfamily plays important roles in cytokine production and stress response. Growth factors such as EGF (Epidermal Growth Factor) or proinflammatory cytokines such as IL (Interleukin) and TNF (Tumor Necrosis Factor) stimulate p38 signaling. Numerous physical and chemical stresses, including hormones, UV irradiation, ischemia, osmotic shock and heat shock can also activate p38 MAPKs. In addition, oxidative stress and GPCR stimulation indirectly activate p38.

p38 MAPKs regulate downstream targets including several kinases, transcription factors and cytosolic proteins. These kinases include MAPKAPK2 (MAPK-Activated Protein Kinase-2), MAPKAPK3 (MAPK-Activated Protein Kinase-3), PRAK (p38-Related/Activated Protein Kinase), MSK1 (Mitogen- and Stress-Activated Protein Kinase-1) and MNK 1/2 (MAP kinase-interacting kinase 1/2). Some important transcription factors phosphorylated by p38 include tumor suppressor protein p53, CHOP (C/EBP-Homologous Protein), STAT1 (Signal Transducers and Activators of Transcription-1), CREB (cAMP Response Element-Binding Protein), and Max/Myc complexes, etc.

Click gene symbol on the map to view ORF/cDNA clone.

Data source: KEGG, BioCarta