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Activation of phospholipase C by α_(1-)adrenergic receptors is mediated by the α subunits of Gq family

Wu, Dianqing and Katz, Arieh and Lee, Chang Ho and Simon, Melvin I. (1992) Activation of phospholipase C by α_(1-)adrenergic receptors is mediated by the α subunits of Gq family. Journal of Biological Chemistry, 267 (36). pp. 25798-25802. ISSN 0021-9258. http://resolver.caltech.edu/CaltechAUTHORS:20120330-093740454

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Abstract

High efficiency transient transfection of Cos-7 cells was previously used to establish the functional coupling between Gαq/Gα11 and phospholipase C β_1 (Wu, D., Lee, C-H., Rhee, S. G., and Simon, M. I. (1992) J. Biol. Chem. 267, 1811-1817). Here the same system was used to study the functional coupling between other guanine nucleotide-binding regulatory protein (G-protein) α subunits and phospholipases and to study which Gα subunits mediate the activation of phospholipase C by the α_1-adrenergic receptor subtypes, α_1A, α_1B, and α_1C. We found that Gα14 and Gα16 behaved like Gα11 or Gαq, i.e. they could activate endogenous phospholipases in Cos-7 cells in the presence of AIFn. The synergistic increase in inositol phosphate release in Cos-7 cells after they were cotransfected with cDNAs encoding Gα subunits and phospholipase C β_1 indicates that both Gα 16 and Gα14 can activate phospholipase C β_1. The activation of phospholipase C β_1 was restricted to members of the Gq subfamily of α subunits. They activated phospholipase C β_1 but not phospholipase C γ1, γ2, or phospholipase C δ3. The cotransfection of Cos-7 cells with cDNAs encoding three different α1-adrenergic receptors and Gαq or Gα11 leads to an increase in norepinephrine-dependent inositol phosphate release. This indicates that Gαq or Gα11 can mediate the activation of phospholipase C by all three subtypes of α_1-adrenergic receptors. With the same assay system, Gα16 and Gα14 appear to be differentially involved in the activation of phospholipase C by the α_1-adrenergic receptors. The α_1B subtype receptor gave a ligand-mediated synergistic response in the cells cotransfected with either Gα14 or Gα16. However, the α_1C receptor responded in cells cotransfected with Gα14 but not Gα16, and the α_1A receptor showed little synergistic response in cells transfected with either Gα14 or Gα16. The ability of the α_1A and α_1C receptors to activate phospholipase C through Gαq and Gα11 was also demonstrated in a cell-free system. Clearly Gαq and Gα ll can couple all three of the α_1-adrenergic receptors to activate phospholipase C β_1, however, there are differences in the relative coupling of the Gαl4 and Gαl6 subunits to these receptors.


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Additional Information:© 1992 American Society for Biochemistry and Molecular Biology, Inc. Received for publication, May 28, 1992. This work was supported by United States Public Health Services Grant GM34236 (to M. I. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. We thank Drs. Thomas Wilkie and Huiping Jiang for critical reading of this manuscript, Drs. Robert J. Lefkowitz and Susanna Cotecchia for the α_1-AR cDNAs, and Joyce Kato for help in preparing the manuscript.
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U. S. Public Health Service (USPHS)GM34236
Record Number:CaltechAUTHORS:20120330-093740454
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20120330-093740454
Official Citation:Activation of phospholipase C by α1-adrenergic receptors is mediated by the α subunits of Gq family. D Wu, A Katz, C H Lee, and M I Simon J. Biol. Chem. 1992 267: 25798-802.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:29909
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:30 Mar 2012 19:05
Last Modified:30 Mar 2012 19:05

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