Editors' ChoiceG Proteins

Convergent Paths

Science's STKE  29 Aug 2000:
Vol. 2000, Issue 47, pp. tw9
DOI: 10.1126/stke.2000.47.tw9

G protein-coupled receptors can couple to more than one G protein. Blaukat et al. provide evidence for the requirement of two G protein pathways in signaling from bradykinin and muscarinic acetylcholine receptors to the mitogen-activated protein kinase (MAPK) cascade. Receptors and a hemagglutinin-tagged version of the MAPK, extracellular signal-regulated kinase 2 (ERK2), were transfected into HEK293 cells, and then the Gαi and the Gαq/11 pathways were blocked pharmacologically or by coexpression of dominant-negative proteins involved in the relevant pathway. The data suggest that bradykinin activates Ras through Gαi but that activation of the mitogen-activated and ERK kinase (MEK) downstream of Ras requires activation of the Gαq/11 pathway as well. These results were confirmed in human foreskin fibroblasts, which also depended on intact Gαi and Gαq/11 pathways for bradykinin-stimulated MAPK activation. Fibroblasts from Gαq/11-deficient mice also failed to activate MAPK in response to bradykinin. Thus, two G protein pathways may need to converge to lead to specific cellular responses from a single activated receptor.

Blaukat, A., Barac, A., Cross, M.J., Offermanns, S., and Dikic, I. (2000) G protein-coupled receptor-mediated mitogen-activated protein kinase activation through cooperation of Gαq and Gαi signals. Mol. Cell. Biol. 20: 6837-6848. [Abstract] [Full Text]