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Originally published In Press as doi:10.1074/jbc.C000322200 on June 5, 2000

J. Biol. Chem., Vol. 275, Issue 31, 23421-23424, August 4, 2000
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ACCELERATED PUBLICATION
Activation of Heterotrimeric G-protein Signaling by a Ras-related Protein
IMPLICATIONS FOR SIGNAL INTEGRATION*

Mary J. CismowskiDagger §||, Chienling MaDagger ||, Catalina Ribas, Xiaobing XieDagger ||, Michael Spruyt||, Jeffrey S. LizanoDagger ||, Stephen M. Lanier, and Emir DuzicDagger ||**

From Dagger  OSI Pharmaceuticals, Tarrytown, New York 10591, the  Department of Pharmacology, Medical University of South Carolina, Charleston, South Carolina 29425, and || Cadus Pharmaceutical Corporation, Tarrytown, New York 10591

Utilizing a functional screen in the yeast Saccharomyces cerevisiae we identified mammalian proteins that activate heterotrimeric G-protein signaling pathways in a receptor-independent fashion. One of the identified activators, termed AGS1 (for activator of G-protein signaling), is a human Ras-related G-protein that defines a distinct subgroup of the Ras superfamily. Expression of AGS1 in yeast and in mammalian cells results in specific activation of Galpha i/Galpha o heterotrimeric signaling pathways. In addition, the in vivo and in vitro properties of AGS1 are consistent with it functioning as a direct guanine nucleotide exchange factor for Galpha i/Galpha o. AGS1 thus presents a unique mechanism for signal integration via heterotrimeric G-protein signaling pathways.

* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

This work was supported in part by National Institutes of Health Grant RO1-NS24821 (to S. M. L.).

§ To whom correspondence should be addressed. Present address: Neurocrine Biosciences, Inc., 10555 Science Center Dr., San Diego, CA 92121. E-mail: mcismowski@neurocrine.com.

** Present address: Millenium Pharmaceuticals Inc., 270 Albany St., Cambridge, MA 02139.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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