Signaling Pathways Activating p38 MAPK

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• Reviews
• Pathway Key
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Pathway Description:

p38 MAPKs (α, β, γ and δ) are members of the MAPK family that are activated by a variety of environmental stresses and inflammatory cytokines. As with other MAPK cascades, the membrane-proximal component is a MAPKKK, typically a MEKK or a mixed lineage kinase (MLK). The MAPKKK phosphorylates and activates MKK3/6, the p38 MAPK kinases. MKK3/6 can also be activated directly by ASK1, which is stimulated by apoptotic stimuli. p38 MAPK is involved in regulation of HSP27 and MK2 (MAPKAPK-2), MK3 (MAPKAPK-3) and several transcription factors including ATF-2, Stat1, the Max/Myc complex, MEF-2, Elk-1 and indirectly CREB via activation of MSK1.

Selected Reviews:

• Ashwell JD (2006) The many paths to p38 mitogen-activated protein kinase activation in the immune system. Nat. Rev. Immunol. 6(7), 532–40.
• Bradham C, McClay DR (2006) p38 MAPK in development and cancer. Cell Cycle 5(8), 824–8.
• Clerk A, Sugden PH (2006) Inflame my heart (by p38-MAPK). Circ. Res. 99(5), 455–8.
• Cook R, Wu CC, Kang YJ, Han J (2007) The role of the p38 pathway in adaptive immunity. Cell. Mol. Immunol. 4(4), 253–9.
• Cuenda A, Rousseau S (2007) p38 MAP-kinases pathway regulation, function and role in human diseases. Biochim. Biophys. Acta 1773(8), 1358–75.

CST would like to thank Prof. John Blenis, Harvard Medical School, Boston, Massachusetts, for reviewing this diagram.