G-Protein-Coupled Receptors Signaling to MAPK/Erk
Pathway Description:
G-protein-coupled receptors (GPCRs) are activated by a wide variety of external stimuli. Upon receptor activation, the G-protein exchanges GDP for GTP, causing the dissociation of the GTP-bound α and β/γ subunits and triggering diverse signaling cascades. Receptors coupled to different heterotrimeric G-protein subtypes can utilize different scaffolds to activate the small G-protein/MAPK cascade, employing at least three different classes of Tyr kinases. Src family kinases are recruited following activation of PI3Kγ by β/γ subunits. They are also recruited by receptor internalization, cross-activation of receptor Tyr kinases, or by signaling through an integrin scaffold involving Pyk2 and/or FAK. GPCRs can also employ PLCβ to mediate activation of PKC and CaMKII, which can have either stimulatory or inhibitory consequences for the downstream MAPK pathway.
Selected Reviews:
- Caunt CJ, Finch AR, Sedgley KR, McArdle CA (2006) Seven-transmembrane receptor signalling and ERK compartmentalization. Trends Endocrinol. Metab. 17(7), 276–83.
- Dikic I, Blaukat A (1999) Protein tyrosine kinase-mediated pathways in G protein-coupled receptor signaling. Cell Biochem. Biophys. 30(3), 369–87.
- Marinissen MJ, Gutkind JS (2001) G-protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol. Sci. 22(7), 368–76.
- Pierce KL, Luttrell LM, Lefkowitz RJ (2001) New mechanisms in heptahelical receptor signaling to mitogen activated protein kinase cascades. Oncogene 20(13), 1532–9.
CST would like to thank Prof. John Blenis, Harvard Medical School, Boston, Massachusetts, for reviewing this diagram.
created October 2002 • revised December 2006
