Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas

Abstract 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 o...

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Autores principales:	Isabel Weigand, Cristina L. Ronchi, Marthe Rizk-Rabin, Guido Di Dalmazi, Vanessa Wild, Kerstin Bathon, Beatrice Rubin, Davide Calebiro, Felix Beuschlein, Jérôme Bertherat, Martin Fassnacht, Silviu Sbiera
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a7dfc728130647c9871d28bac6b0b73e
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spelling	oai:doaj.org-article:a7dfc728130647c9871d28bac6b0b73e2021-12-02T16:06:58ZDifferential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas10.1038/s41598-017-00125-82045-2322https://doaj.org/article/a7dfc728130647c9871d28bac6b0b73e2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00125-8https://doaj.org/toc/2045-2322Abstract 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.Isabel WeigandCristina L. RonchiMarthe Rizk-RabinGuido Di DalmaziVanessa WildKerstin BathonBeatrice RubinDavide CalebiroFelix BeuschleinJérôme BertheratMartin FassnachtSilviu SbieraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Isabel Weigand Cristina L. Ronchi Marthe Rizk-Rabin Guido Di Dalmazi Vanessa Wild Kerstin Bathon Beatrice Rubin Davide Calebiro Felix Beuschlein Jérôme Bertherat Martin Fassnacht Silviu Sbiera Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas
description	Abstract 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	article
author	Isabel Weigand Cristina L. Ronchi Marthe Rizk-Rabin Guido Di Dalmazi Vanessa Wild Kerstin Bathon Beatrice Rubin Davide Calebiro Felix Beuschlein Jérôme Bertherat Martin Fassnacht Silviu Sbiera
author_facet	Isabel Weigand Cristina L. Ronchi Marthe Rizk-Rabin Guido Di Dalmazi Vanessa Wild Kerstin Bathon Beatrice Rubin Davide Calebiro Felix Beuschlein Jérôme Bertherat Martin Fassnacht Silviu Sbiera
author_sort	Isabel Weigand
title	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_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_sort	differential expression of the protein kinase a subunits in normal adrenal glands and adrenocortical adenomas
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a7dfc728130647c9871d28bac6b0b73e
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Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas

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