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Overview of MAP Kinase Signaling

MAP Kinase Signaling

Mitogen-activated protein kinases (MAPKs) are a highly conserved family of serine/threonine protein kinases involved in a variety of fundamental cellular processes such as proliferation, differentiation, motility, stress response, apoptosis, and survival. Conventional MAPKs include the extracellular signal-regulated kinase 1 and 2 (Erk1/2 or p44/42), the c-Jun N-terminal kinases 1-3 (JNK1-3)/ stress activated protein kinases (SAPK1A, 1B, 1C), the p38 isoforms (p38α, β, γ, and δ), and Erk5. The lesser-studied, atypical MAPKs include Nemo-like kinase (NLK), Erk3/4, and Erk7/8.

A broad range of extracellular stimuli including mitogens, cytokines, growth factors, and environmental stressors stimulate the activation of one or more MAPKK kinases (MAPKKKs) via receptor-dependent and -independent mechanisms. MAPKKKs then phosphorylate and activate a downstream MAPK kinase (MAPKK), which in turn phosphorylates and activates MAPKs. Activation of MAPKs leads to the phosphorylation and activation of specific MAPK-activated protein kinases (MAPKAPKs), such as members of the RSK, MSK, or MNK family, and MK2/3/5. These MAPKAPKs function to amplify the signal and mediate the broad range of biological processes regulated by the different MAPKs. While most MAPKKK, MAPKK, and MAPKs display a strong preference for one set of substrates, there is significant cross-talk in a stimulus and cell-type dependent manner.


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