Signaling Pathways Activating p38 MAPK

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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, MAPKAPK-2 (MK2), MAPKAPK-3 (MK3), 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:

    Coulthard LR, White DE, Jones DL, McDermott MF, Burchill SA (2009) p38(MAPK): stress responses from molecular mechanisms to therapeutics. Trends Mol Med15(8), 369–79.
    Cuadrado A, Nebreda AR (2010) Mechanisms and functions of p38 MAPK signalling. Biochem. J.429(3), 403–17.
    del Barco Barrantes I, Nebreda AR (2012) Roles of p38 MAPKs in invasion and metastasis.Biochem. Soc. Trans. 40(1), 79–84.
    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.
    Kostenko S, Dumitriu G, Lægreid KJ, Moens U (2011) Physiological roles of mitogen-activated-protein-kinase-activated p38-regulated/activated protein kinase. World J Biol Chem 2(5), 73–89.
    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.

created January 2003

 

revised October 2012