Mechanisms of Aberrant PKA Activation by Cα Subunit Mutations
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Mechanisms of Aberrant PKA Activation by Cα Subunit Mutations. / Calebiro, Davide; Bathon, K.; Weigand, I.
In: Hormone and Metabolic Research, Vol. 49, No. 4, 01.04.2017, p. 307-314.Research output: Contribution to journal › Review article › peer-review
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TY - JOUR
T1 - Mechanisms of Aberrant PKA Activation by Cα Subunit Mutations
AU - Calebiro, Davide
AU - Bathon, K.
AU - Weigand, I.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
KW - cAMP
KW - Cushing's syndrome
KW - PRKACA mutation
UR - http://www.scopus.com/inward/record.url?scp=84994634525&partnerID=8YFLogxK
U2 - 10.1055/s-0042-112817
DO - 10.1055/s-0042-112817
M3 - Review article
AN - SCOPUS:84994634525
VL - 49
SP - 307
EP - 314
JO - Hormone and Metabolic Research
JF - Hormone and Metabolic Research
SN - 0018-5043
IS - 4
ER -