Signaling in Time and Space: Localizing PKA to Macromolecular Signaling Complexes

A major mechanism for achieving specificity in PKA signaling is through localization to specific sites in the cell. One of the most important mechanisms for localizing PKA is through A Kinase Anchoring Proteins (AKAPs) that bind to the dimerization domain of the PKA regulatory subunits. We show how an amphipathic helix in the AKAP docks with high affinity to the helical dimerization domain of the regulatory subunit and then targets it to different sites such as a channel, a transporter, or the mitochondria. There the docked PKA functions as part of a large and dynamic macromolecular complex that regulates events such channel opening or closing, Internalization of the transporter, or fission/fusion of the mitochondria.