MAPK/Erk in Growth and Differentiation

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Search this pathway for protein information from PhosphoSitePlus^®, our expert-curated knowledge base of protein phosphorylation and other post-translational modifications.

Pathway Description:

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.
• Dhillon AS, Hagan S, Rath O, Kolch W (2007) MAP kinase signalling pathways in cancer. Oncogene 26(22), 3279–90.
• Keyse SM (2008) Dual-specificity MAP kinase phosphatases (MKPs) and cancer. Cancer Metastasis Rev. 27(2), 253–61.
• Kim EK, Choi EJ (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim. Biophys. Acta 1802(4), 396–405.
• McKay MM, Morrison DK (2007) Integrating signals from RTKs to ERK/MAPK. Oncogene 26(22), 3113–21.
• Pullikuth AK, Catling AD (2007) Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: a perspective. Cell. Signal. 19(8), 1621–32.
• Tidyman WE, Rauen KA (2009) The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. Curr. Opin. Genet. Dev. 19(3), 230–6.
• Zhang Y, Dong C (2007) Regulatory mechanisms of mitogen-activated kinase signaling. Cell. Mol. Life Sci. 64(21), 2771–89.

We would like to thank Prof. John Blenis, Harvard Medical School, Boston, MA, for reviewing this diagram.