Pharmacological PKA Inhibition: All May Not Be What It Seems

Sci. Signal.  03 Jun 2008:
Vol. 1, Issue 22, pp. re4
DOI: 10.1126/scisignal.122re4
Fig. 1.

Summary of the cAMP signaling cascade. cAMP is produced from ATP by adenylyl cyclase and is broken down by phosphodiesterases to 5′ AMP. Adenylyl cyclase activity can be modulated by agonist binding at GPCRs. cAMP acts directly on three targets: PKA, Epac, and CNGCs. These in turn regulate various cellular processes both directly and through intermediaries. For clarity, a number of pathways mediated by PKA, Epac, and Rap1 have been omitted. These pathways are discussed more fully in (1, 6, 8, 9, 63). AKAP, A-kinase anchoring protein; ATF1, activating transcription factor 1; C, protein kinase A catalytic subunit; cAMP, cyclic adenosine monophosphate; CNGC, cyclic nucleotide–gated ion channel; CREB, cAMP response element–binding protein; CREM, cAMP response element modulator; ERK1/2, extracellular signal–related kinase 1/2; JNK, Jun N-terminal kinase; PDE, phosphodiesterases; PKA, protein kinase A; R, protein kinase A regulatory subunit