A-Kinase Anchoring proteins (AKAPs) tether the cAMP dependent protein kinase, PKA, and other enzymes to distinct subcellular locations providing a mechanism by which cells organize the correct repertoires of enzymes in individual signaling pathways. AKAP79/150 is a neuronalty expressed AKAP that coordinates a signaling cornplex containing protein kinase A (PKA), protein kinase C (PKC) and the phosphatase PP2B in the postsynaptic density. Preliminary data indicate that AKAP79/150 may also interact with DARPP32, a dopamine and cAMP regulated phosphoprotein that is an inhibitor of the type 1 phosphatase (PP1). PKA phosphorylation of DARPP32 converts it into a potent inhibitor of PP1. Dephosphorylation of DARPP32 by PP2B reverses this process. Interestingly both enzymes are anchored by AKAP79/150. Therefore, the specific aims of this proposal are to 1) further characterize DARP32 interaction with AKAP79/150 and 2) determine whether anchoring of PKA facilitates the phosphorylation of DARPP-32 leading to inhibition of PP1. ? ?
| Bauman, Andrea L; Soughayer, Joseph; Nguyen, Bao T et al. (2006) Dynamic regulation of cAMP synthesis through anchored PKA-adenylyl cyclase V/VI complexes. Mol Cell 23:925-31 |
| Bauman, Andrea L; Goehring, April S; Scott, John D (2004) Orchestration of synaptic plasticity through AKAP signaling complexes. Neuropharmacology 46:299-310 |
