The Mitogen-activated protein kinase (MAPK) pathway is a cellular pathway consisting of a large number of proteins that can be activated by a variety of extracellular stimuli. Activation of the MAPK pathway can result in a multitude of physiological effects, including apoptosis, cell proliferation, mitosis, and the transcription of several classes of genes. Although the specific intermediates of the MAPK pathway can vary dramatically depending on physiological state, cell type, and stimuli, the classical MAPK pathway operates in the following general sequence: external growth factors bind to a transmembrane protein receptor and this signal is propagated through RAS and Raf intermediates prior to phosphorylating three or more MAPKs in sequence. The MAPK pathway’s ubiquitous nature ensures that this pathway mediates the vast majority of cellular responses.
Aberrant MAPK activity, including constitutive activation or down-regulation, can lead to continuous and unregulated cellular proliferation or muted responses to external stimuli. As a result of its potential influence on such a wide variety of cellular processes, including signal transduction, amplification, and proliferation, the MAPK signaling pathway has been implicated in a broad range of diseases ranging from cancer to obesity. For instance, in many cancers, constitutively active MAPK signaling pathway components such as Ras and Raf induce cell proliferation in the absence of appropriate signals. Raf mutations have been identified in melanomas, thyroid, colorectal, and ovarian cancers. Current research is focused on creating and evaluating the efficacy of many downstream MAPK modulators and inhibitors.
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