Subunits beta gamma of heterotrimeric G protein activate beta 2 isoform of phospholipase C.
The activation of heterotrimeric G proteins results in the exchange of GDP bound to the alpha-subunit for GTP and the subsequent dissociation of a complex of the beta- and gamma-subunits (G beta gamma). The alpha-subunits of different G proteins interact with a variety of effectors, but less is known about the function of the free G beta gamma complex. G beta gamma has been implicated in the activation of a cardiac potassium channel, a retinal phospholipase A2 (ref. 9) and a specific receptor kinase, and in vitro reconstitution experiments indicate that the G beta gamma complex can act with G alpha subunit to modulate the activity of different isoforms of adenylyl cyclase. Of two phospholipase activities that can be separated in extracts of HL-60 cells, purified G beta gamma is found to activate one of them. Here we report that in co-transfection assays G beta gamma subunits specifically activate the beta 2 and not the beta 1 isoform of phospholipase, which acts on phosphatidylinositol. We use transfection assays to show also that receptor-mediated release of G beta gamma from G proteins that are sensitive to pertussis toxin can result in activation of the phospholipase. This effect may be the basis of the pertussis-toxin-sensitive phospholipase C activation seen in some cell systems (reviewed in refs 13 and 14).
Katz
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Division of Biology, California Institute of Technology, Pasadena 91125.
Wu
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Simon
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D037361:Adenylate Cyclase Toxin; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D003600:Cytosol / Q000201:enzymology; D004247:DNA / Q000235:genetics; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D037342:Pertussis Toxin; D015398:Signal Transduction; D014162:Transfection; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D007295:Inositol Phosphates; D007527:Isoenzymes; D046911:Macromolecular Substances; D010566:Virulence Factors, Bordetella; D007294:Inositol; D002217:Carbachol; D004247:DNA; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins