The role of AKAP12 in coordination of VEGF‐induced endothelial cell motility

The role of AKAP12 in coordination of VEGF-induced endothelial cell motilityIn this issue of Acta Physiologica, Benz et al study the role of one important protein in the cyclic AMP signalling pathway, the A-kinase anchoring (AKAP)12.1 The downstream effects stemming from cAMP release are tightly controlled and activate a profusion of signalling pathways.However, many of these different processes function with largely the same major constituent proteins, including adenylate cyclases, kinases, phosphatases and phosphodiesterases.cAMP-dependent protein kinase (PKA), which is the main intracellular target for cAMP, is widely found in these signalling assemblies, and is present at high concentrations in many tissues, playing varied roles in the regulation of molecular processes.Unexpectedly, despite its ubiquity there are only four isoforms of PKA regulatory subunit with which to impart functional and locational specificity.However, we have increasingly come to understand that signalling interactions are governed not only by the global abundance of proteins in a cell, but also from their interactions with each other in organized subcellular microdomains, which mediate spatial and temporal precision into signalling events.These microdomains are largely coordinated by scaffolding proteins, which regulate processes by binding to and localizing the interacting proteins in fixed relationships to one another and to the subcellular architecture.Through these interactions scaffolding proteins dictate where, when and how molecular signalling events progress.Control of PKA localization is defined not only by differences in its own isoforms, but also by its association with a diverse class of scaffolding proteins containing around 50 members, known as AKAPs. 2 Although the presence of a PKA binding site designates these proteins as AKAPs, the name belies the important role they often play in binding additional proteins and synchronizing large multi-member complexes, which serve to integrate signals from diverse pathways.AKAP12, alternatively known as gravin or SSeCKS, binds selectively to one of the two types of PKA regulatory subunits, that is, the type II regulatory subunit, as well as to other proteins including protein kinase C (PKC), calmodulin, Src ORCID