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J Biol Chem, Vol. 274, Issue 31, 21507-21510, July 30, 1999

COMMUNICATION
Modulation of Rap Activity by Direct Interaction of G_o with Rap1 GTPase-activating Protein

J. Dedrick Jordan, Kendall D. Carey^¶, Philip J. S. Stork^¶, and Ravi Iyengar

From the  Department of Pharmacology, Mount Sinai School of Medicine, New York, New York 10029 and ^¶ The Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201

We used the yeast two-hybrid system to identify proteins that interact directly with G_o. Mutant-activated G_o was used as the bait to screen a cDNA library from chick dorsal root ganglion neurons. We found that G_o interacted with several proteins including Gz-GTPase-activating protein (Gz-GAP), a new RGS protein (RGS-17), a novel protein of unknown function (IP6), and Rap1GAP. This study focuses on Rap1GAP, which selectively interacts with G_o and G_i but not with G_s or G_q. Rap1GAP interacts more avidly with the unactivated G_o as compared with the mutant (Q205L)-activated G_o. When expressed in HEK-293 cells, unactivated G_o co-immunoprecipitates with the Rap1GAP. Expression of chick Rap1GAP in PC-12 cells inhibited activation of Rap1 by forskolin. When unactivated G_o was expressed, the amount of activated Rap1 was greatly increased. This effect was not observed with the Q205L-G_o. Expression of unactivated G_o stimulated MAP-kinase (MAPK1/2) activity in a Rap1GAP-dependent manner. These results identify a novel function of G_o, which in its resting state can sequester Rap1GAP thereby regulating Rap1 activity and consequently gating signal flow from Rap1 to MAPK1/2. Thus, activation of G_o could modulate the Rap1 effects on a variety of cellular functions.

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Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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