Signaling Pathways Activating p38 MAPK

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Search this pathway for protein information from PhosphoSitePlus^®, our expert-curated knowledge base of protein phosphorylation and other post-translational modifications.

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.
• Coulthard LR, White DE, Jones DL, McDermott MF, Burchill SA (2009) p38(MAPK): stress responses from molecular mechanisms to therapeutics. Trends Mol Med 15(8), 369–79.
• Cuenda A, Rousseau S (2007) p38 MAP-kinases pathway regulation, function and role in human diseases. Biochim. Biophys. Acta 1773(8), 1358–75.
• Huang G, Shi LZ, Chi H (2009) Regulation of JNK and p38 MAPK in the immune system: signal integration, propagation and termination. Cytokine 48(3), 161–9.
• Shiryaev A, Moens U (2010) Mitogen-activated protein kinase p38 and MK2, MK3 and MK5: ménage à trois or ménage à quatre? Cell. Signal. 22(8), 1185–92.

We would like to thank Prof. John Blenis, Harvard Medical School, Boston, MA, for contributing to this diagram.