Analysis of Kinase and Phosphatase Signaling Complexes

Oregon Health And Science University, Portland OR

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Abstract

[unreadable] DESCRIPTION (provided by applicant): 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. [unreadable] [unreadable]