Adenylyl cyclase--A-kinase anchoring protein complexes: the next dimension in cAMP signaling

The formation of multiprotein complexes is a repeated theme in biology ranging from the regulation of the extracellular signal-regulated kinase and cAMP signaling pathways to the formation of postsynaptic density complexes or tight junctions. A-kinase anchoring proteins (AKAPs) are well known for their ability to scaffold protein kinase A and components upstream and downstream of cAMP production, including G protein-coupled receptors, cAMP-dependent Rap-exchange factors, and phosphodiesterases. Specific adenylyl cyclase (AC) isoforms have also been identified as components of AKAP complexes, namely AKAP79, Yotiao, and mAKAP. In this review, we summarize recent evidence for AC-AKAP complexes and requirements for compartmentalization of cAMP signaling. The ability of AKAPs to assemble intricate feedback loops to control spatiotemporal aspects of cAMP signaling adds yet another dimension to the classic cAMP pathway.