MAPK/Erk in Growth and Differentiation

• Description
• Reviews
• Pathway Key
• Pathway Products
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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:

• Giancotti FG, Ruoslahti E (1999) Integrin signaling. Science 285(5430), 1028–32.
• Kolch W (2005) Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat. Rev. Mol. Cell Biol. 6(11), 827–37.
• Lewis TS, Shapiro PS, Ahn NG (1998) Signal transduction through MAP kinase cascades. Adv. Cancer Res. 74, 49–139.
• Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH (2001) Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr. Rev. 22(2), 153–83.
• Porter AC, Vaillancourt RR (1998) Tyrosine kinase receptor-activated signal transduction pathways which lead to oncogenesis. Oncogene 17(11 Reviews), 1343–52.
• Rane SG (1999) Ion channels as physiological effectors for growth factor receptor and Ras/ERK signaling pathways. Adv. Second Messenger Phosphoprotein Res. 33, 107–27.
• Roux PP, Blenis J (2004) ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev. 68(2), 320–44.
• Stork PJ, Schmitt JM (2002) Crosstalk between cAMP and MAP kinase signaling in the regulation of cell proliferation. Trends Cell Biol. 12(6), 258–66.
• Pouyssegur J, Volmat V, Lenormand P (2002) Fidelity and spatio-temporal control in MAP kinase (ERKs) signalling. Biochem. Pharmacol. 64(5-6), 755–63.

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

created January 2003 • revised January 2007