Mechanisms of Aberrant PKA Activation by Cα Subunit Mutations
Research output: Contribution to journal › Review article › peer-review
Authors
Colleges, School and Institutes
External organisations
- Rudolf Virchow Center
- University of Würzburg
- University of Wurzburg
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.
Details
Original language | English |
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Pages (from-to) | 307-314 |
Number of pages | 8 |
Journal | Hormone and Metabolic Research |
Volume | 49 |
Issue number | 4 |
Early online date | 3 Nov 2016 |
Publication status | Published - 1 Apr 2017 |
Keywords
- cAMP, Cushing's syndrome, PRKACA mutation