1. Nat. Rev. Endocrinol. doi:10.1038/nrendo.2016.24
Figure 3 Disruption of the cAMP–PKA signalling pathway in adrenocortical cells occurs in several endocrine disorders
Figure 3 | Disruption of the cAMP–PKA signalling pathway in adrenocortical cells occurs in several endocrine disorders. a | In normal physiology of an adrenocortical cell in the resting state, protein kinase A (PKA) exists as an inactive tetramer comprising a dimer of regulatory subunits bound to catalytic subunits. Phosphodiesterases (PDEs) act as inhibitors of the pathway by degrading cAMP in order to regulate signal transduction. b | In McCune–Albright syndrome, activating mutations in the GNAS gene, which encodes the stimulatory guanine nucleotide-binding protein (Gsα) subunit, lead to constitutive activation of the Gsα protein subunit that couples hormone receptors to intracellular generation of cAMP. Mutations in Gsα lead to prolonged activation of Gsα and its downstream effectors. Adenylyl cyclase catalyses the conversion of ATP to cAMP, and elevation in cellular cAMP levels leads to activation of PKA, release of the catalytic subunits and phosphorylation of downstream targets, including the transcription factor cAMP response-element binding protein (CREB). c | In Carney complex, inactivating mutations in the regulatory subunit 1α of PKA (R1α) subunit of PKA lead to suppression of its inhibitory action, release of the catalytic subunits and transcription of downstream targets. d | Inactivating mutations in phosphodiesterases lead to accumulation of cAMP and dysregulated activation of the cAMP–PKA pathway. e | Activating mutations in the catalytic subunit of PKA result in upregulation of the PKA pathway and phosphorylation of downstream targets. AC, adenylyl cyclase; Cα, catalytic subunit of PKA; GPCR, G-protein-coupled receptor.
Lodish, M. & Stratakis, C. A. (2016) A genetic and molecular update on adrenocortical causes of Cushing syndrome
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