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Chromodomain Helicase Binding Protein 8 (Chd8) Is a Novel A-Kinase Anchoring Protein Expressed during Rat Cardiac Development

A-kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) and localize the holoenzyme to discrete signaling microdomains in multiple subcellular compartments. Despite emerging evidence for a nuclear pool of PKA that rapidly responds to activation of the PKA signaling...

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Autores principales: Shanks, Maureen O., Lund, Linda M., Manni, Sabrina, Russell, Mary, Mauban, Joseph R. H., Bond, Meredith
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468582/
https://www.ncbi.nlm.nih.gov/pubmed/23071553
http://dx.doi.org/10.1371/journal.pone.0046316
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author Shanks, Maureen O.
Lund, Linda M.
Manni, Sabrina
Russell, Mary
Mauban, Joseph R. H.
Bond, Meredith
author_facet Shanks, Maureen O.
Lund, Linda M.
Manni, Sabrina
Russell, Mary
Mauban, Joseph R. H.
Bond, Meredith
author_sort Shanks, Maureen O.
collection PubMed
description A-kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) and localize the holoenzyme to discrete signaling microdomains in multiple subcellular compartments. Despite emerging evidence for a nuclear pool of PKA that rapidly responds to activation of the PKA signaling cascade, only a few AKAPs have been identified that localize to the nucleus. Here we show a PKA-binding domain in the amino terminus of Chd8, and demonstrate subcellular colocalization of Chd8 with RII. RII overlay and immunoprecipitation assays demonstrate binding between Chd8-S and RIIα. Binding is abrogated upon dephosphorylation of RIIα. By immunofluorescence, we identified nuclear and perinuclear pools of Chd8 in HeLa cells and rat neonatal cardiomyocytes. We also show high levels of Chd8 mRNA in RNA extracted from post-natal rat hearts. These data add Chd8 to the short list of known nuclear AKAPs, and implicate a function for Chd8 in post-natal rat cardiac development.
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spelling pubmed-34685822012-10-15 Chromodomain Helicase Binding Protein 8 (Chd8) Is a Novel A-Kinase Anchoring Protein Expressed during Rat Cardiac Development Shanks, Maureen O. Lund, Linda M. Manni, Sabrina Russell, Mary Mauban, Joseph R. H. Bond, Meredith PLoS One Research Article A-kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) and localize the holoenzyme to discrete signaling microdomains in multiple subcellular compartments. Despite emerging evidence for a nuclear pool of PKA that rapidly responds to activation of the PKA signaling cascade, only a few AKAPs have been identified that localize to the nucleus. Here we show a PKA-binding domain in the amino terminus of Chd8, and demonstrate subcellular colocalization of Chd8 with RII. RII overlay and immunoprecipitation assays demonstrate binding between Chd8-S and RIIα. Binding is abrogated upon dephosphorylation of RIIα. By immunofluorescence, we identified nuclear and perinuclear pools of Chd8 in HeLa cells and rat neonatal cardiomyocytes. We also show high levels of Chd8 mRNA in RNA extracted from post-natal rat hearts. These data add Chd8 to the short list of known nuclear AKAPs, and implicate a function for Chd8 in post-natal rat cardiac development. Public Library of Science 2012-10-10 /pmc/articles/PMC3468582/ /pubmed/23071553 http://dx.doi.org/10.1371/journal.pone.0046316 Text en © 2012 Shanks et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Shanks, Maureen O.
Lund, Linda M.
Manni, Sabrina
Russell, Mary
Mauban, Joseph R. H.
Bond, Meredith
Chromodomain Helicase Binding Protein 8 (Chd8) Is a Novel A-Kinase Anchoring Protein Expressed during Rat Cardiac Development
title Chromodomain Helicase Binding Protein 8 (Chd8) Is a Novel A-Kinase Anchoring Protein Expressed during Rat Cardiac Development
title_full Chromodomain Helicase Binding Protein 8 (Chd8) Is a Novel A-Kinase Anchoring Protein Expressed during Rat Cardiac Development
title_fullStr Chromodomain Helicase Binding Protein 8 (Chd8) Is a Novel A-Kinase Anchoring Protein Expressed during Rat Cardiac Development
title_full_unstemmed Chromodomain Helicase Binding Protein 8 (Chd8) Is a Novel A-Kinase Anchoring Protein Expressed during Rat Cardiac Development
title_short Chromodomain Helicase Binding Protein 8 (Chd8) Is a Novel A-Kinase Anchoring Protein Expressed during Rat Cardiac Development
title_sort chromodomain helicase binding protein 8 (chd8) is a novel a-kinase anchoring protein expressed during rat cardiac development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468582/
https://www.ncbi.nlm.nih.gov/pubmed/23071553
http://dx.doi.org/10.1371/journal.pone.0046316
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