New insights into the regulation of cAMP synthesis beyond GPCR/G protein activation: Implications in cardiovascular regulation

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.