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

Autor:	Hermann JS; Department of Biochemistry, University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany., Skroblin P; Anchored Signaling, Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch, Robert-Rössle-Str. 10, 13125 Berlin, Germany., Bertinetti D; Department of Biochemistry, University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany., Hanold LE; Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, 240 W. Green St., Athens, GA 30602, United States., von der Heide EK; Department of Biochemistry, University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany., Wagener EM; Department of Biochemistry, University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany., Zenn HM; Department of Biochemistry, University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany., Klussmann E; Anchored Signaling, Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch, Robert-Rössle-Str. 10, 13125 Berlin, Germany; DZHK, German Centre for Cardiovascular Research, Oudenarder Straße 16, 13347 Berlin, Germany., Kennedy EJ; Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, 240 W. Green St., Athens, GA 30602, United States., Herberg FW; Department of Biochemistry, University of Kassel, Heinrich-Plett-Strasse 40, 34132 Kassel, Germany. Electronic address: herberg@uni-kassel.de.
Jazyk:	angličtina
Zdroj:	Biochimica et biophysica acta [Biochim Biophys Acta] 2015 Oct; Vol. 1854 (10 Pt B), pp. 1667-75. Date of Electronic Publication: 2015 Apr 23.
DOI:	10.1016/j.bbapap.2015.04.018
Abstrakt:	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 RIIα subunit of PKA with nanomolar affinity. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases. (Copyright © 2015 Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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