Inhibition of catalytic unit of adenylate cyclase and activation of GTPase of Ni protein by beta gamma-subunits of GTP-binding proteins.
A protein factor which inhibited adenylate cyclase was purified to apparent homogeneity from rat brain and identified as the beta gamma-subunits of the GTP-binding regulatory proteins of adenylate cyclase. (i) The beta gamma-subunits (protein factor) inhibited the partially purified catalytic unit of adenylate cyclase in the presence of an activator, forskolin or the stimulative regulatory protein (Ns), to 60 and 40% of the control, respectively; inhibition of the catalytic unit in the presence of forskolin required no guanine nucleotides. (ii) The subunits enhanced the GTPase activity of the purified alpha-subunit of the inhibitory regulatory protein (Ni alpha) 3.8-fold. (iii) The subunits stimulated ADP-ribosylation of Ni alpha catalyzed by islet-activating protein (pertussis toxin). ADP-ribosylation had no effect on the GTPase activity of Ni alpha in the presence of the beta gamma-subunits. The results suggest that direct inhibition of the catalytic unit by the beta gamma-subunits liberated from Ni is essential for the receptor-mediated inhibition of adenylate cyclase.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001923:Brain Chemistry; D002384:Catalysis; D002850:Chromatography, Gel; D005576:Colforsin / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D037342:Pertussis Toxin; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000378:metabolism
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D037342:Pertussis Toxin; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins