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Inhibition of Subsets of G Protein-coupled Receptors by Empty Mutants of G Protein α Subunits in Go, G11, and G16

Yu, Bo and Gu, Lingjie and Simon, Melvin I. (2000) Inhibition of Subsets of G Protein-coupled Receptors by Empty Mutants of G Protein α Subunits in Go, G11, and G16. Journal of Biological Chemistry, 275 (1). pp. 71-76. ISSN 0021-9258. https://resolver.caltech.edu/CaltechAUTHORS:YUBjbc00

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Abstract

We previously reported that the xanthine nucleotide binding Goα mutant, GoαX, inhibited the activation of Gi-coupled receptors. We constructed similar mutations in G11α and G16α and characterized their nucleotide binding and receptor interaction. First, we found that G11αX and G16αX expressed in COS-7 cells bound xanthine 5'-O-(thiotriphosphate) instead of guanosine 5'-O-(thiotriphosphate). Second, we found that G11αX and G16αX interacted with βγ subunits in the presence of xanthine diphosphate. These experiments demonstrated that G11aαX and G16αX were xanthine nucleotide-binding proteins, similar to GoαX. Third, in COS-7 cells, both G11αX and G16αX inhibited the activation of Gq-coupled receptors, whereas only G16αX inhibited the activation of Gi-coupled receptors. Therefore, when in the nucleotide-free state, empty G11αX and G16αX appeared to retain the same receptor binding specificity as their wild-type counterparts. Finally, we found that GoαX, G11αX, and G16αX all inhibited the endogenous thrombin receptors and lysophosphatidic acid receptors in NIH3T3 cells, whereas G11αX and G16αX, but not GoαX, inhibited the activation of transfected m1 muscarinic receptor in these cells. We conclude that these empty G protein mutants of Goα, G11α, and G16α can act as dominant negative inhibitors against specific subsets of G protein-coupled receptors.


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Additional Information:Copyright © 2000 by the American Society for Biochemistry and Molecular Biology. (Received for publication, September 1, 1999) 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.
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Deposited On:21 Dec 2008 03:00
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