An investigation of PKA phosphorylation gradients and a mechanism for their enhancement

The cAMP dependent protein kinase, or protein kinase A (PKA) is an important and ubiquitous intracellular mediator of information transfer in neurons, where it plays critical roles in neurotransmission, cellular excitability, and synaptic plasticity. All of these processes require high specificity in PKA phosphorylation. An abundance of studies have shown that PKA specificity is mediated by a class of proteins called A-kinase anchoring proteins (AKAPs), which target upstream activators, downstream substrates, and inhibitors of PKA to defined subcellular locations, putatively establishing tight gradients of PKA phosphorylation. However, AKAPs directly anchor only the regulatory subunit of PKA.