title: New insights into the regulation of cAMP synthesis beyond GPCR/G protein activation: implications in cardiovascular regulation.
abstract: Regulation of intracellular concentrations of cyclic AMP is one of the most ubiquitous mechanisms for regulating cellular functions. Further, the manner in which cAMP production is regulated via G proteins at the level of adenylyl cyclase activation has been studied extensively. This review focuses instead on the recently identified mechanisms and roles for regulation of adenylyl cyclase functions beyond G protein activation. These mechanisms include: a) the coupling of particular isoforms of adenylyl cyclase to function within a single cell type b) regulation of membrane trafficking of higher order enzyme aggregates and c) raf kinase-dependent phosphorylation and sensitization of adenylyl cyclases--an important pathway for crosstalk between tyrosine kinase signaling cascades with regulation of cAMP-mediated responses.
authors.affiliation: Cell Biology and Vascular Biology Research Groups, Robarts Research Institute, London, Ontario, Canada. feldmanr@lhsc.on.ca
authors.forename: Ross D
authors.initials: RD
authors.lastname: Feldman
authors.forename: Robert
authors.initials: R
authors.lastname: Gros
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D002302:Cardiac Output; D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006333:Heart Failure / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D009097:Multienzyme Complexes; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D009097:Multienzyme Complexes; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP; D019908:Proto-Oncogene Proteins c-raf; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6