Mechanisms of Aberrant PKA Activation by Cα Subunit Mutations

Davide Calebiro, K. Bathon, I. Weigand

Research output: Contribution to journalReview articlepeer-review

10 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)307-314
Number of pages8
JournalHormone and Metabolic Research
Issue number4
Early online date3 Nov 2016
Publication statusPublished - 1 Apr 2017


  • cAMP
  • Cushing's syndrome
  • PRKACA mutation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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