Journal article
Neurochondrin is an atypical RII alpha-specific A-kinase anchoring protein
Publication Details
Authors: | Hermann, J.; Skroblin, P.; Bertinetti, D.; Bertinetti, D.; von der Heide, E.; Wagener, E.; Zenn, H.; Klussmann, E.; Kennedy, E.; Herberg, F. |
Publisher: | ELSEVIER SCIENCE BV |
Publication year: | 2015 |
Journal: | Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics |
Pages range : | 1667-1675 |
Volume number: | 1854 |
Issue number: | 10 |
Start page: | 1667 |
End page: | 1675 |
Number of pages: | 9 |
ISSN: | 1570-9639 |
eISSN: | 1878-1454 |
DOI-Link der Erstveröffentlichung: |
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/docldng (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 PICA through a novel mechanism that involves two distinct binding regions. In addition, we demonstrate that neurochondrin has strong isoform selectivity towards the Hot subunit of PKA with nanomolar affinity. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (C) 2015 Elsevier B.V. All rights reserved.
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/docldng (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 PICA through a novel mechanism that involves two distinct binding regions. In addition, we demonstrate that neurochondrin has strong isoform selectivity towards the Hot subunit of PKA with nanomolar affinity. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (C) 2015 Elsevier B.V. All rights reserved.
Keywords
A-kinase anchoring proteins, Neurochondrin, Protein kinase A, RII-specific
