Mitogen-Activated Protein Kinase
Mitogen-activated protein kinase (MAPK) pathways are major signal transduction routes that transfer and amplify messages from the cell surface to the nucleus, producing a range of cellular effects, eg, cell proliferation. There are several distinct MAPK pathways, important in the regulation of cell proliferation, differentiation, development, inflammation, survival, and migration. In transformed cells, the Ras-Raf-MEK-ERK pathway has been implicated in uncontrolled cell proliferation and survival.
The Ras-Raf-MEK-ERK pathway is activated by a range of growth factor receptors (including EGFR, platelet-derived growth factor receptor, type-1 insulin-like growth factor receptor, and fibroblast growth factor receptor). The pathway can also be activated by cytokines, steroid hormones, and several agonists that act via G-protein-coupled receptors. Growth-factor stimulation of the Ras-Raf-MEK-ERK pathway leads to sequential activation of Ras and Raf, which in turn activate MAPK kinase 1 and 2 (MEK 1/2).1 MEK 1/2 is a dual-specificity kinase that is essential to the propagation of growth factor signaling and is known to amplify signals to extracellular signal-regulated kinase 1 and 2 (ERK 1/2), also known as MAPK 1/2, that in turn can phosphorylate and activate a range of proteins, including several transcription factors.
Constitutive activation of the Ras-Raf-MEK-ERK pathway has been demonstrated in several cancer types, including pancreatic, colon, lung, and melanoma. Inhibition of this pathway via MEK 1/2 is an attractive strategy for therapeutic intervention in cancer because it has the potential to block inappropriate signal transduction regardless of the upstream position of the oncogenic aberration. Furthermore, ERK 1/2 are the only known substrates for MEK 1/2.
Constitutive activation of the Ras-Raf-MEK-ERK pathway has been observed in several cancer types, including pancreatic, colon, lung, and melanoma. See how inhibition of this pathway via MEK 1/2 might contribute to therapeutic intervention in cancer. Click the play button below.
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