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Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas
Somatic mutations in protein kinase A catalytic α subunit (PRKACA) were found to be causative for 30–40% of cortisol-producing adenomas (CPA) of the adrenal gland, rendering PKA signalling constitutively active. In its resting state, PKA is a stable and inactive heterotetramer, consisting of two cat...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427838/ https://www.ncbi.nlm.nih.gov/pubmed/28250426 http://dx.doi.org/10.1038/s41598-017-00125-8 |
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author | Weigand, Isabel Ronchi, Cristina L. Rizk-Rabin, Marthe Dalmazi, Guido Di Wild, Vanessa Bathon, Kerstin Rubin, Beatrice Calebiro, Davide Beuschlein, Felix Bertherat, Jérôme Fassnacht, Martin Sbiera, Silviu |
author_facet | Weigand, Isabel Ronchi, Cristina L. Rizk-Rabin, Marthe Dalmazi, Guido Di Wild, Vanessa Bathon, Kerstin Rubin, Beatrice Calebiro, Davide Beuschlein, Felix Bertherat, Jérôme Fassnacht, Martin Sbiera, Silviu |
author_sort | Weigand, Isabel |
collection | PubMed |
description | Somatic mutations in protein kinase A catalytic α subunit (PRKACA) were found to be causative for 30–40% of cortisol-producing adenomas (CPA) of the adrenal gland, rendering PKA signalling constitutively active. In its resting state, PKA is a stable and inactive heterotetramer, consisting of two catalytic and two regulatory subunits with the latter inhibiting PKA activity. The human genome encodes three different PKA catalytic subunits and four different regulatory subunits that are preferentially expressed in different organs. In normal adrenal glands all regulatory subunits are expressed, while CPA exhibit reduced protein levels of the regulatory subunit IIβ. In this study, we linked for the first time the loss of RIIβ protein levels to the PRKACA mutation status and found the down-regulation of RIIβ to arise post-transcriptionally. We further found the PKA subunit expression pattern of different tumours is also present in the zones of the normal adrenal cortex and demonstrate that the different PKA subunits have a differential expression pattern in each zone of the normal adrenal gland, indicating potential specific roles of these subunits in the regulation of different hormones secretion. |
format | Online Article Text |
id | pubmed-5427838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-54278382017-05-12 Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas Weigand, Isabel Ronchi, Cristina L. Rizk-Rabin, Marthe Dalmazi, Guido Di Wild, Vanessa Bathon, Kerstin Rubin, Beatrice Calebiro, Davide Beuschlein, Felix Bertherat, Jérôme Fassnacht, Martin Sbiera, Silviu Sci Rep Article Somatic mutations in protein kinase A catalytic α subunit (PRKACA) were found to be causative for 30–40% of cortisol-producing adenomas (CPA) of the adrenal gland, rendering PKA signalling constitutively active. In its resting state, PKA is a stable and inactive heterotetramer, consisting of two catalytic and two regulatory subunits with the latter inhibiting PKA activity. The human genome encodes three different PKA catalytic subunits and four different regulatory subunits that are preferentially expressed in different organs. In normal adrenal glands all regulatory subunits are expressed, while CPA exhibit reduced protein levels of the regulatory subunit IIβ. In this study, we linked for the first time the loss of RIIβ protein levels to the PRKACA mutation status and found the down-regulation of RIIβ to arise post-transcriptionally. We further found the PKA subunit expression pattern of different tumours is also present in the zones of the normal adrenal cortex and demonstrate that the different PKA subunits have a differential expression pattern in each zone of the normal adrenal gland, indicating potential specific roles of these subunits in the regulation of different hormones secretion. Nature Publishing Group UK 2017-03-13 /pmc/articles/PMC5427838/ /pubmed/28250426 http://dx.doi.org/10.1038/s41598-017-00125-8 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Weigand, Isabel Ronchi, Cristina L. Rizk-Rabin, Marthe Dalmazi, Guido Di Wild, Vanessa Bathon, Kerstin Rubin, Beatrice Calebiro, Davide Beuschlein, Felix Bertherat, Jérôme Fassnacht, Martin Sbiera, Silviu Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas |
title | Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas |
title_full | Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas |
title_fullStr | Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas |
title_full_unstemmed | Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas |
title_short | Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas |
title_sort | differential expression of the protein kinase a subunits in normal adrenal glands and adrenocortical adenomas |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427838/ https://www.ncbi.nlm.nih.gov/pubmed/28250426 http://dx.doi.org/10.1038/s41598-017-00125-8 |
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