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Sci. STKE, 30 November 2004
Vol. 2004, Issue 261, p. tw434
[DOI: 10.1126/stke.2612004tw434]


Membrane Trafficking The Inside Story on Gαs

Best known for their role in transducing extracellular signals to the intracellular pathways that mediate their effects, heterotrimeric GTP-binding proteins (G proteins) are also found on intracellular membranes, where they have been hypothesized to play a role in membrane trafficking. Zheng et al., who previously identified RGS-PX1, which acts as a Gαs GTPase activating protein and also as a sorting nexin (SNX, a family of proteins implicated in endosomal trafficking) that affects epidermal growth factor receptor (EGFR) degradation, investigated the role of Gαs in EGFR trafficking. When overexpressed in HEK293 cells also transfected with pXER-EGFR, Gαs enhanced degradation of EGF and the EGFR (following stimulation with EGF). In contrast, Gαs knockdown with siRNA delayed EGFR degradation in Cos7 cells, as did knockdown of the endosomal protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs). Knockdown of both Gαs and Hrs led to a greater delay in EGFR degradation than knockdown of either Gαs or Hrs alone. The authors used glutathione-S-transferase pull-down assays to show that both Gαs and RGS-PX1 bound Hrs in vitro and used coimmunoprecipitation to show that Gαs, RGS-PX1, and Hrs formed a complex in vivo. Gαs transfected into Cos7 cells colocalized with Hrs or RGS-Px1 in endosomes; moreover, overexpression of either RGS-PX1 or Hrs promoted the endosomal localization of Gαs. Thus, Gαs, acting in association with RGS-PX1 and Hrs, appears to play a role in regulating EGFR trafficking and degradation.

B. Zheng, C. Lavoie, T.-D. Tang, P. Ma, T. Meerloo, A. Beas, M. G. Farquhar, Regulation of epidermal growth factor receptor degradation by heterotrimeric Gαs protein. Mol. Biol. Cell 15, 5538-5550 (2004). [Abstract] [Full Text]

Citation: The Inside Story on Gαs. Sci. STKE 2004, tw434 (2004).

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