p38 MAPK, a member of the mitogen-activated protein kinase (MAPK) family, is activated by a variety of environmental stresses and inflammatory cytokines. p38 MAPK family includes p38α, p38β, p38γ, and p38δ. This pathway plays a crucial role in the regulation of cellular responses to stress, inflammation, and immune function. The p38 MAPK pathway is initiated by MAPK kinase kinases (MAPKKKs), such as MEKK or MLK, which phosphorylate and activate MAPK kinases (MAPKKs) like MKK3/6. These, in turn, phosphorylate and activate p38 MAPK. Downstream of p38 MAPK, a number of substrates are regulated, including HSP27, MAPKAPK-2 (MK2), MAPKAPK-3 (MK3), and various transcription factors like ATF-2, Stat1, Max/Myc complex, MEF-2, and Elk-1. This signaling pathway is involved in a wide range of biological processes, from the regulation of gene expression to cell cycle control, apoptosis, and autophagy. The p38 MAPK pathway is also implicated in the pathogenesis of various diseases, including cancer, where it can act as either a promoter or suppressor of tumor growth and metastasis, depending on the cellular context.
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