title: 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 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.
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Weigand
authors.affiliation: Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Ronchi
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR810, Department of Endocrinology, Reference Center for Rare Adrenal diseases, Assistance Publique Hôpiteaux de Paris, Hôpital Cochin, Descartes University, Paris, France.
authors.forename: Marthe
authors.initials: M
authors.lastname: Rizk-Rabin
authors.affiliation: Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Guido Di
authors.initials: GD
authors.lastname: Dalmazi
authors.affiliation: Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Wild
authors.affiliation: Institute of Pharmacology and Toxicology and Bioimaging Center, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bathon
authors.affiliation: Endocrinology Unit, Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Rubin
authors.affiliation: Institute of Pharmacology and Toxicology and Bioimaging Center, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Davide
authors.initials: D
authors.lastname: Calebiro
authors.affiliation: Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Felix
authors.identifier: 0000-0001-7826-3984
authors.initials: F
authors.lastname: Beuschlein
authors.affiliation: Institut Cochin, INSERM U1016, CNRS UMR810, Department of Endocrinology, Reference Center for Rare Adrenal diseases, Assistance Publique Hôpiteaux de Paris, Hôpital Cochin, Descartes University, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany.|Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany.|Central Laboratory, University Hospital, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg, Wuerzburg, Germany. Sbiera_S@ukw.de.|Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany. Sbiera_S@ukw.de.
authors.forename: Silviu
authors.initials: S
authors.lastname: Sbiera
mesh_terms: D000311:Adrenal Glands / Q000502:physiology*; D018246:Adrenocortical Adenoma / Q000473:pathology*; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000032:analysis* / Q000235:genetics; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit / Q000032:analysis*; D020869:Gene Expression Profiling; D006801:Humans
chemical_list: D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; C517837:PRKAR2B protein, human; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; C517757:PRKACA protein, human