Transient complexes. A new structural model for the activation of adenylate cyclase by hormone receptors (guanine nucleotides/irradiation inactivation).
1. The irradiation-inactivation procedure was used to study changes in the state of association of the protein components of adenylate cyclase in intact rat liver plasma membranes by measurement of alterations in the target size determined from the catalytic activity of the enzyme. 2. A decrease in target size at 30 degrees C in response to p[NH]ppG (guanosine 5'-[betagamma-imido]triphosphate) or GTP was demonstrated, which we take to reflect the dissociation of a regulatory subunit. The effect of GTP is potentiated by glucagon. This effect is not observed at 0 degrees C. 3. An increase in target size was observed in response to glucagon in the absence of guanine nucleotides, which we take to reflect the association of glucagon receptor with adenylate cyclase. 4. We propose a model for the activation of adenylate cyclase by glucagon in which the binding of the hormone to its receptor causes an initial association of the receptor with the catalytic unit of the enzyme and a regulatory subunit to form a ternary complex. The subsequent activation of the adenylate cyclase results from the dissociation of the ternary complex to leave a free catalytic unit in the activated state. This dissociation requires the binding of a guanine nucleotide to the regulatory subunit. 5. The effects of variation of temperature on the activation of adenylate cyclase by glucagon and guanine nucleotides were examined and are discussed in relation to the irradiation-activation data. 6. The effectiveness of hormones, guanine nucleotides and combinations of hormone and guanine nucleotides as activators of adenylate cyclase in both rat liver and rat fat-cell plasma membranes was studied and the results are discussed in relation to the model proposed, which is also considered in relation to the observations published by other workers.
D000262:Adenylyl Cyclases / Q000378:metabolism* / Q000528:radiation effects; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D005934:Glucagon / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D046911:Macromolecular Substances; D008954:Models, Biological; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*
D006728:Hormones; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D005934:Glucagon; D000262:Adenylyl Cyclases