The ascent of AKAPs, from architectural elements to kinase anchors: a perspective.

Abstract

Protein interaction domains binding to their recognition motifs are the nuts and bolts that hold macromolecular complexes together. Point mutations and gene fusions that drive evolutionary changes in these interactors have created a burgeoning repertoire of protein scaffolds. A-Kinase anchoring proteins (AKAPs) are archetypal signal organizing proteins that compartmentalize protein kinase A (PKA) inside the cell. An amino-terminal docking and dimerization (d/d) domain on the regulatory subunit of the kinase binds with high affinity to an amphipathic helix on the AKAP. This perspective introduces a new group of interactors called docking and dimerization domain interacting proteins that preceded the advent of the AKAP-PKA interface. We also examine various evolutionary paths used by anchoring proteins to gain PKA binding function.