p38 MAPK signaling pathway

p38 MAPKs are members of the MAPK family that are activated by a variety of environmental stresses and inflammatory cytokines. Stress signals are delivered to this cascade by members of small GTPases of the Rho family (Rac, Rho, Cdc42). 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 activated MKK3/5, the p38 MAPK kinase. MKK3/6 can also be activated directly by ASK1, which is stimulated by apoptotic stimuli. P38 MAK is involved in regulation of Hsp27 and MAPKAP-2 and several transcription factors including ATF2, STAT1, THE Max/Myc complex, MEF-2, ELK-1 and indirectly CREB via activation of MSK1.

p38 MAPKs是MAPK家族的成员，它们可被多种环境压力和炎症细胞因子激活。通过Rho家族的小GTPase成员（如Rac、Rho、Cdc42）传递的应激信号作用于这一级联反应。与其他MAPK级联反应类似，膜邻近成分是一个MAPKKK，通常是MEKK或混合谱系激酶（MLK）。MAPKKK通过磷酸化并激活MKK3/5，即p38 MAPK激酶。MKK3/6还可直接由ASK1激活，而ASK1受到凋亡刺激的刺激。P38 MAK参与调节Hsp27和MAPKAP-2，以及包括ATF2、STAT1、Max/Myc复合体、MEF-2、ELK-1在内的多种转录因子，并间接通过MSK1的激活影响CREB。