MAPK/Erk in Growth and Differentiation
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The MAPK/Erk signaling cascade is activated by a wide variety of receptors involved in growth and differentiation including receptor tyrosine kinases (RTKs), integrins, and ion channels. The specific components of the cascade vary greatly among different stimuli, but the architecture of the pathway usually includes a set of adaptors (Shc, GRB2, Crk, etc.) linking the receptor to a guanine nucleotide exchange factor (SOS, C3G, etc.) transducing the signal to small GTP-binding proteins (Ras, Rap1), which in turn activate the core unit of the cascade composed of a MAPKKK (Raf), a MAPKK (MEK1/2), and MAPK (Erk). An activated Erk dimer can regulate targets in the cytosol and also translocate to the nucleus where it phosphorylates a variety of transcription factors regulating gene expression.
Selected Reviews:
- Anjum R, Blenis J (2008) The RSK family of kinases: emerging roles in cellular signalling. Nat. Rev. Mol. Cell Biol. 9(10), 747–58.
- Kim EK, Choi EJ (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim. Biophys. Acta 1802(4), 396–405.
- Keyse SM (2008) Dual-specificity MAP kinase phosphatases (MKPs) and cancer. Cancer Metastasis Rev. 27(2), 253–61.
- De Luca A, Maiello MR, D'Alessio A, Pergameno M, Normanno N (2012) The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin. Ther. Targets 16 Suppl 2, S17–27.
- Mendoza MC, Er EE, Blenis J (2011) The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem. Sci. 36(6), 320–8.
- Romeo Y, Zhang X, Roux PP (2012) Regulation and function of the RSK family of protein kinases. Biochem. J. 441(2), 553–69.
- Roskoski R (2012) MEK1/2 dual-specificity protein kinases: structure and regulation. Biochem. Biophys. Res. Commun. 417(1), 5–10.
- Tidyman WE, Rauen KA (2009) The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. Curr. Opin. Genet. Dev. 19(3), 230–6.
We would like to thank Prof. John Blenis, Harvard Medical School, Boston, MA, for reviewing this diagram.
created January 2003
revised October 2012