Mitogen-Activated Protein Kinase Cascades

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Pathway Description:

Mitogen-activated protein kinases (MAPK) are a family of Ser/Thr protein kinases widely conserved among eukaryotes and are involved in many cellular programs such as cell proliferation, cell differentiation, cell movement, and cell death. MAPK signaling cascades are organized hierarchically into three-tiered modules. MAPKs are phosphorylated and activated by MAPK-kinases (MAPKKs), which in turn are phosphorylated and activated by MAPKK-kinases (MAPKKKs). The MAPKKKs are in turn activated by interaction with the family of small GTPases and/or other protein kinases, connecting the MAPK module to cell surface receptors or external stimuli.

Selected Reviews:

• Junttila MR, Li SP, Westermarck J (2008) Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival. FASEB J. 22(4), 954–65.
• Murphy LO, Blenis J (2006) MAPK signal specificity: the right place at the right time. Trends Biochem. Sci. 31(5), 268–75.
• Pimienta G, Pascual J (2007) Canonical and alternative MAPK signaling. Cell Cycle 6(21), 2628–32.
• Raman M, Chen W, Cobb MH (2007) Differential regulation and properties of MAPKs. Oncogene 26(22), 3100–12.
• Turjanski AG, Vaqué JP, Gutkind JS (2007) MAP kinases and the control of nuclear events. Oncogene 26(22), 3240–53.
• Zhang Y, Dong C (2007) Regulatory mechanisms of mitogen-activated kinase signaling. Cell. Mol. Life Sci. 64(21), 2771–89.