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Horm Metab Res 2017; 49(04): 307-314
DOI: 10.1055/s-0042-112817
Review

Mechanisms of Aberrant PKA Activation by Cα Subunit Mutations

D. Calebiro
1   Institute of Pharmacology and Toxicology, University Hospital, University of Würzburg, Würzburg, Germany
2   Bio-Imaging Center/Rudolf Virchow Center, University of Würzburg, Würzburg, Germany
,
K. Bathon
1   Institute of Pharmacology and Toxicology, University Hospital, University of Würzburg, Würzburg, Germany
2   Bio-Imaging Center/Rudolf Virchow Center, University of Würzburg, Würzburg, Germany
,
I. Weigand
3   Department of Medicine I, Endocrine and Diabetes Unit, University Hospital, University of Würzburg, Würzburg, Germany
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Abstract

Somatic mutations in PRKACA, coding for the catalytic α subunit of protein kinase A (PKA), have been recently identified as the most frequent genetic alteration in cortisol-secreting adrenocortical adenomas, which are responsible for adrenal Cushing’s syndrome. The mutations identified so far lie at the interface between the catalytic (C) and regulatory (R) subunit of PKA. Detailed functional studies of the most frequent of these mutations (L206R) as well as of another one in the same region of the C subunit (199_200insW) have revealed that these mutations cause constitutive activation of PKA and lack of regulation by cAMP. This is due to interference with the binding of the R subunit, which keeps the C subunit inactive in the absence of cyclic AMP. Here, we review these recent findings, with a particular focus on the mechanisms of action of PRKACA mutations.

Key words

PRKACA mutation - Cushing’s syndrome - cAMP


Publikationsverlauf

Eingereicht: 04. Mai 2016

Angenommen: 14. Juli 2016

Artikel online veröffentlicht:
03. November 2016

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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