| Modification Notes |
Adenylyl cyclases function to convert ATP to cyclic AMP in response to activa-tion by a variety of hormones, neurotransmitters and other regulatory molecules. Cyclic AMP, in turn, activates several other target molecules to control a broad range of diverse phenomena such as metabolism, gene transcription and memory. Adenylyl cyclases respond to receptor-initiated signals, mediated by the Gs and Gi heterotrimeric G proteins. The binding of an agonist to a Gs coupled receptor catalyzes the exchange of GDP (bound to Ga s) for GTP, the dissociation of GTP-Ga s from Gbg and Ga s-mediated activation of adenylyl cyclase. Adenylyl cyclases of the type II family differ from other subforms in that they are conditionally stimulated by Ga s/bg subunits and regulated by PKC-mediated C-terminal phosphorylation. Both short- and long-term activation of D(2L) dopamine receptors result in a marked degree of sensitization of A cyclase I, II, V and IX, but not A cyclase VIII. The effects on A cyclase I, II and VIII is dependent upon the ability of these A cyclase isoforms to synergistically respond to selective activators in the presence of activated Ga s. |