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