G PROTEINS Convergent Paths

Abstract:

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 G_i and the G_q/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 G_i but that activation of the mitogen-activated and ERK kinase (MEK) downstream of Ras requires activation of the G_q/11 pathway as well. These results were confirmed in human foreskin fibroblasts, which also depended on intact G_i and G_q/11 pathways for bradykinin-stimulated MAPK activation. Fibroblasts from G_q/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 G_q and G_i signals. Mol. Cell. Biol. 20: 6837-6848. [Abstract] [Full Text]