cAMP-stimulated adenylate cyclase activation in Dictyostelium discoideum is inhibited by agents acting at the cell surface.
The ability of Dictyostelium discoideum amoebae to synthesize and secrete cAMP in response to exogenous cAMP is called cAMP signaling. Concanavalin A is a potent, rapid, noncompetitive inhibitor of this response, with the rate of inhibition consistent with its rate of binding. The concanavalin A does not deplete cellular ATP, alter cAMP binding to its surface receptors, or affect basal adenylate cyclase activity, but blocks the cAMP-stimulated activation of adenylate cyclase. Therefore, concanavalin A appears to inhibit a step between the receptor and the adenylate cyclase which is necessary for the transduction of the cAMP signal. Wheat germ agglutinin, a polyclonal antibody against an 80-kDa glycoprotein, four monoclonal antibodies against the amoebal surface, and a chemical cross-linking agent which reacts with cell surface primary amines also inhibit signaling. To determine the importance of cross-linking in the inhibition, succinylated concanavalin A and the unlinked, reactive portion of the chemical cross-linker were tested and found to be relatively ineffective inhibitors. Thus it appears that ligands capable of cross-linking molecules on the external surface of D. discoideum amoebae inhibit cAMP signaling. It is proposed that these cross-linking agents prevent membrane or cytoskeletal rearrangement and that this rearrangement must occur before the adenylate cyclase is activated.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004023:Dictyostelium / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D037102:Lectins / Q000494:pharmacology; D013388:Succinimides / Q000494:pharmacology; D013499:Surface Properties; D013997:Time Factors; D014909:Wheat Germ Agglutinins
D003432:Cross-Linking Reagents; D037102:Lectins; D013388:Succinimides; D014909:Wheat Germ Agglutinins; D003208:Concanavalin A; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C011240:dithiobis(succinimidylpropionate)