Offermanns, Stefan and Simon, Melvin I. (1995) Gα15 and Gα16 Couple a Wide Variety of Receptors to Phospholipase C. Journal of Biological Chemistry, 270 (25). pp. 15175-15180. ISSN 0021-9258. http://resolver.caltech.edu/CaltechAUTHORS:OFFjbc95
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The murine G-protein α-subunit Gα15 and its human counterpart Gα16 are expressed in a subset of hematopoietic cells, and they have been shown to regulate β-isoforms of inositide-specific phospholipase C. We studied the ability of a variety of receptors to interact with Gα15 and Gα16 by cotransfecting receptors and G-protein α-subunits in COS-7 cells. Activation of β2 adrenergic and muscarinic M2 receptors in cells expressing the receptors alone or together with Gαq, Gα11, or Gα14 led to a very small stimulation of endogenous phospholipase C. However, when the receptors were coexpressed with Gα15 and Gα16, addition of appropriate ligands caused a severalfold increase in inositol phosphate production which was time- and dose-dependent. A similar activation of phospholipase C was observed when several other receptors which were previously shown to couple to members of the Gi and Gs family were coexpressed with Gα15/16. In addition, stimulation of inositol phosphate formation via receptors naturally coupled to phospholipase C was enhanced by cotransfection of Gα15 and Gα16. These data demonstrate that Gα15 and Gα16 are unique in that they can be activated by a wide variety of G-protein-coupled receptors. The ability of Gα15 and Gα16 to bypass the selectivity of receptor G-protein interaction can be a useful tool to understand the mechanism of receptor-induced G-protein activation. In addition, the promiscuous behavior of Gα15 and Gα16 toward receptors may be helpful in finding ligands corresponding to orphan receptors whose signaling properties are unknown.
|Additional Information:||© 1995 by The American Society for Biochemistry and Molecular Biology, Inc. (Received for publication, March 27, 1995) We thank Drs. Michael J. Brownstein, Marc G. Caron, Shaun R. Coughlin, Masakazu Hirata, Robert J. Lefkowitz, Ernest G. Peralta, Peter R. Schofield, and Lei Yu for providing expression plasmids of receptors. This work was supported by Grant GM34236 from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. [S.O. was the] [r]ecipient of a fellowship from the Deutsche Forschungsgemeinschaft.|
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