p38 MAPKs 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 kinase. MKK3/6 can also be activated directly by ASK1, which is stimulated by apoptotic stimuli. p38 MAPK is involved in regulation of HSP27 and MAPKAP-2 and several transcription factors including ATF-2, Stat1, the Max/Myc complex, MEF-2, Elk-1 and indirectly CREB via activation of MSK1
