Figure 1.

cAMP signaling. (A) In normal adrenocortical cells, ACTH binds to its G-coupled receptor, MC2R. This leads to the activation of adenylate cyclase (AC), which convert ATP into cAMP. cAMP then binds the regulatory (R) subunit of PKA, inducing the release of the catalytic subunit (C). The catalytic subunit phosphorylates its downstream target such as CREB, which in turn induces the expression of genes involved in cortisol synthesis. (B) In adrenocortical adenoma cells producing cortisol autonomously with PRKACA mutations (star), the catalytic (C) subunit of PKA is unable to interact with the regulatory subunit (R). The unregulated PRKACA may now mediate its serine-threonine kinase activity without any restrains.