G alpha 15 and G alpha 16 couple a wide variety of receptors to phospholipase C.
The murine G-protein alpha-subunit G alpha 15 and its human counterpart G alpha 16 are expressed in a subset of hematopoietic cells, and they have been shown to regulate beta-isoforms of inositide-specific phospholipase C. We studied the ability of a variety of receptors to interact with G alpha 15 and G alpha 16 by cotransfecting receptors and G-protein alpha-subunits in COS-7 cells. Activation of beta 2 adrenergic and muscarinic M2 receptors in cells expressing the receptors alone or together with G alpha q, G alpha 11, or G alpha 14 led to a very small stimulation of endogenous phospholipase C. However, when the receptors were coexpressed with G alpha 15 and G alpha 16, 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 G alpha 15/16. In addition, stimulation of inositol phosphate formation via receptors naturally coupled to phospholipase C was enhanced by cotransfection of G alpha 15 and G alpha 16. These data demonstrate that G alpha 15 and G alpha 16 are unique in that they can be activated by a wide variety of G-protein-coupled receptors. The ability of G alpha 15 and G alpha 16 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 G alpha 15 and G alpha 16 toward receptors may be helpful in finding ligands corresponding to orphan receptors whose signaling properties are unknown.
Offermanns
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S
Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Simon
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MI
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis / Q000502:physiology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000096:biosynthesis / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000096:biosynthesis / Q000502:physiology*; D018000:Receptors, Peptide / Q000096:biosynthesis / Q000502:physiology*; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000378:metabolism
D007295:Inositol Phosphates; D046911:Macromolecular Substances; D018343:Receptors, Adrenergic, beta-2; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D011976:Receptors, Muscarinic; D017450:Receptors, Opioid, mu; D018000:Receptors, Peptide; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D002217:Carbachol; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D001616:beta-Galactosidase; D019204:GTP-Binding Proteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D007545:Isoproterenol