Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger that directs a plethora of cellular processes. In the cardiovascular system, cAMP, for example modulates contractility of cardiac myocytes and participates in the control of blood pressure through vascular smooth muscle cell
Protein kinase A (PKA) is a ubiquitous serine/threonine kinase that controls a large variety of cellular functions. Specificity of PKA action is achieved by controlling its cellular localization through A-kinase anchoring proteins (AKAPs). AKAPs bind PKA through an amphipathic α-helical structure (RII-binding domain), which interacts directly with the dimerization and docking (D/D) domain of regulatory subunit dimers. Besides PKA, AKAPs directly bind other signalling proteins such as other protein kinases, protein phosphatases, phosphodiesterases (PDEs), GTPases, adaptor proteins and substrate proteins of PKA through unique interacting domains. Thus AKAPs coordinate multi-protein signalling complexes establishing compartmentalized signalling.
Our aim is to elucidate the role and the molecular mechanisms of compartmentalized cAMP/PKA signalling in controlling vasopressin-mediated water reabsorption in renal principal cells and cardiac myocyte contractility.