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Sci. STKE, 5 November 2002
Vol. 2002, Issue 157, p. tw400
[DOI: 10.1126/stke.2002.157.tw400]

EDITORS' CHOICE

G PROTEIN-COUPLED RECEPTORS ß-AR Recruits a Ras Activator

Pak et al. report that the COOH-terminal (Ser-X-Val or Leu) SkV motif of the ß1-adrenergic receptor (ß1-AR) interacts with the cyclic nucleotide Ras guanine nucleotide exchange factor (CN-RasGEF) to stimulate Ras and to cause activation of the mitogen-activated protein kinase (MAPK) cascade. The receptor and GEF colocalize in transfected cells and cells in which the two proteins are endogenously coexpressed, They can also be coprecipitated and interact in glutathione S-transferase pull-down experiments. Futhermore, disruption of their interaction through expression of ß1-ARs with mutations in the SkV motif block activation of Ras. Activation of Ras by the ß1-AR requires the cyclic nucleotide-binding domain and the CDC25 domain of the CN-RasGEF and requires the activity of the G{alpha}s subunit of the heterotrimeric G protein, but not the activity of the Gß{gamma} subunits. Thus, it appears that the ß1-AR recruits the CN-RasGEF to the membrane where the G{alpha}s stimulates local production of cAMP, allowing the CN-RasGEF to be activated and stimulate Ras.

Y. Pak, N. Pham, D. Rotin, Direct binding of the ß1adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activation. Mol. Cell. Biol. 22, 7942-7952 (2002). [Abstract] [Full Text]

Citation: ßAR Recruits a Ras Activator. Sci. STKE 2002, tw400 (2002).



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Science Signaling. ISSN 1937-9145 (pre-2008: Science's STKE. ISSN 1525-8882)