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Science 294 (5548): 1939-1942

Copyright © 2001 by the American Association for the Advancement of Science

RGS-PX1, a GAP for Galpha s and Sorting Nexin in Vesicular Trafficking

Bin Zheng,12* Yong-Chao Ma,5* Rennolds S. Ostrom,3 Christine Lavoie,1 Gordon N. Gill,41 Paul A. Insel,3 Xin-Yun Huang,5 Marilyn G. Farquhar12dagger

Heterotrimeric GTP-binding proteins (G proteins) control cellular functions by transducing signals from the outside to the inside of cells. Regulator of G protein signaling (RGS) proteins are key modulators of the amplitude and duration of G protein-mediated signaling through their ability to serve as guanosine triphosphatase-activating proteins (GAPs). We have identified RGS-PX1, a Galpha s-specific GAP. The RGS domain of RGS-PX1 specifically interacted with Galpha s, accelerated its GTP hydrolysis, and attenuated Galpha s-mediated signaling. RGS-PX1 also contains a Phox (PX) domain that resembles those in sorting nexin (SNX) proteins. Expression of RGS-PX1 delayed lysosomal degradation of the EGF receptor. Because of its bifunctional role as both a GAP and a SNX, RGS-PX1 may link heterotrimeric G protein signaling and vesicular trafficking.

1 Department of Cellular and Molecular Medicine,
2 Department of Pathology,
3 Department of Pharmacology,
4 Department of Medicine, University of California San Diego, La Jolla, CA 92093-0651, USA.
5 Department of Physiology, Weill Medical College of Cornell University, New York, NY 10021, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: mfarquhar{at}ucsd.edu

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