Erk Signaling

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. GPCRs (G-Protein Coupled Receptors) activate the MAPK cascade using a different set of adaptors.

The specific components of the cascade vary greatly among different stimuli, but the architecture of the pathway is similar:

• Adaptors (Shc, GRB2, Crk, etc.) link the receptor to a guanine nucleotide exchange factor (GEF), i.e. SOS and C3G.
• The GEF proteins transduce the signal to small GTP binding proteins (Ras, Rap1).
• The GTP binding protein activates the core unit of the cascade composed of a MAPKKK (Raf), a MAPKK (MEK1/2), and MAPK (Erk). Activated Erk can regulate targets in the cytosol and also translocate to the nucleus where it phosphorylates a variety of transcription factors regulating gene expression.