Classical mitogen-activated protein kinase (MAPK) pathway activation begins at the cell membrane, where small GTPases and various protein kinases phosphorylate and activate MAPKKKs. Subsequently, MAPKKKs directly phosphorylate MAPKKs, which, once activated, phosphorylate MAPKs. Activated MAPKs interact with and phosphorylate numerous cytoplasmic substrates and ultimately modulate transcription factors that drive context-specific gene expression. This, in turn, results in various biological responses, for example osmotic shock, cell cycle progression, or induction of interferon production. There are at least three distinct MAPK signaling modules which mediate extracellular signals into the nucleus to turn on the responsive genes in mammalian cells. These include ERK, JNK, and p38 kinase. The MAPK signaling pathway is essential in regulating many cellular processes including inflammation, cell stress response, cell differentiation, cell division, cell proliferation, metabolism, motility and apoptosis.
Overview of MAPK signaling pathway
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