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J. Biol. Chem. 277 (51): 49888-49895

© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

The beta gamma Subunit of Heterotrimeric G Proteins Interacts with RACK1 and Two Other WD Repeat Proteins*

Edward J. DellDagger , Jennifer ConnorDagger , Songhai Chen§, Elizabeth G. Stebbins, Nikolai P. SkibaDagger , Daria Mochly-Rosen, and Heidi E. HammDagger §||

From the Dagger  Institute for Neuroscience and Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60613, the  Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305-5174, and the § Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600

A yeast two-hybrid approach was used to discern possible new effectors for the beta gamma subunit of heterotrimeric G proteins. Three of the clones isolated are structurally similar to Gbeta , each exhibiting the WD40 repeat motif. Two of these proteins, the receptor for activated C kinase 1 (RACK1) and the dynein intermediate chain, co-immunoprecipitate with Gbeta gamma using an anti-Gbeta antibody. The third protein, AAH20044, has no known function; however, sequence analysis indicates that it is a WD40 repeat protein. Further investigation with RACK1 shows that it not only interacts with Gbeta 1gamma 1 but also unexpectedly with the transducin heterotrimer Galpha tbeta 1gamma 1. Galpha t alone does not interact, but it must contribute to the interaction because the apparent EC50 value of RACK1 for Galpha tbeta 1gamma 1 is 3-fold greater than that for Gbeta 1gamma 1 (0.1 versus 0.3 µM). RACK1 is a scaffold that interacts with several proteins, among which are activated beta IIPKC and dynamin-1 (1). beta IIPKC and dynamin-1 compete with Gbeta 1gamma 1 and Galpha tbeta 1gamma 1 for interaction with RACK1. These findings have several implications: 1) that WD40 repeat proteins may interact with each other; 2) that Gbeta gamma interacts differently with RACK1 than with its other known effectors; and/or 3) that the G protein-RACK1 complex may constitute a signaling scaffold important for intracellular responses.

* This work was supported by Grant EY100291 from the National Institutes of Health (to H. E. H.).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.

|| To whom correspondence should be addressed. Tel.: 615-343-3533; Fax: 615-343-1084; E-mail:

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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