Fig. 1.

(A) Protein kinase A is a central regulatory hub that mediates many physiologic processes, from hormonal growth and metabolism to transport and secretion. (B) Tables display the corresponding protein and gene names for each isoform of regulatory subunit and catalytic subunit. (C) Cartoon rendering of the PKA regulatory and catalytic subunit interactions. The interface of the catalytic subunit’s N-lobe (white) and C-lobe (olive) forms the active site of the kinase, helping to coordinate ATP and substrate. When the regulatory subunit is bound to the catalytic subunit, the inhibitory sequence (IS) occupies the active site to maintain the PKA holoenzyme in its inactive state. PKA exists as a holoenzyme composed of two regulatory and two catalytic subunits, that is coordinated through interactions with the D/D domains, which also bind to AKAPs (see Fig. 5D). When cAMP binds to and inactivates the two cAMP binding domains (CBD-A and CBD-B in teal) of the regulatory subunit, the catalytic subunit is free to phosphorylate its substrates.