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Neurochondrin is an atypical RIIα-specific A-kinase anchoring protein

Item Type:Article
Title:Neurochondrin is an atypical RIIα-specific A-kinase anchoring protein
Creators Name:Hermann, J.S. and Skroblin, P. and Bertinetti, D. and Hanold, L.E. and von der Heide, E.K. and Wagener, E.M. and Zenn, H.M. and Klussmann, E. and Kennedy, E.J. and Herberg, F.W.
Abstract:Protein kinase activity is regulated not only by direct strategies affecting activity but also by spatial and temporal regulatory mechanisms. Kinase signaling pathways are coordinated by scaffolding proteins that orchestrate the assembly of multi-protein complexes. One family of such scaffolding proteins are the A-kinase anchoring proteins (AKAPs). AKAPs share the commonality of binding cAMP-dependent protein kinase (PKA). In addition, they bind further signaling proteins and kinase substrates and tether such multi-protein complexes to subcellular locations. The A-kinase binding (AKB) domain of AKAPs typically contains a conserved helical motif that interacts directly with the dimerization/docking (D/D) domain of the regulatory subunits of PKA. Based on a pull-down proteomics approach, we identified neurochondrin (neurite-outgrowth promoting protein) as a previously unidentified AKAP. Here, we show that neurochondrin interacts directly with PKA through a novel mechanism that involves two distinct binding regions. In addition, we demonstrate that neurochondrin has strong isoform selectivity towards the RII{alpha} subunit of PKA with nanomolar affinity. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.
Keywords:Neurochondrin, A-Kinase Anchoring Proteins, Protein Kinase A, RII-Specific
Source:Biochimica et Biophysica Acta - Proteins and Proteomics
ISSN:1570-9639
Publisher:Elsevier
Volume:1854
Number:10 Pt B
Page Range:1667-1675
Date:October 2015
Additional Information:Copyright © 2015 Elsevier B.V. All rights reserved.
Official Publication:https://doi.org/10.1016/j.bbapap.2015.04.018
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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