Pharmacological PKA Inhibition: All May Not Be What It Seems

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Sci. Signal.  03 Jun 2008:
Vol. 1, Issue 22, pp. re4
DOI: 10.1126/scisignal.122re4
Fig. 3.

Mechanisms of actions of PKA inhibitors. (A) Rp-cAMPS is a competitive antagonist of the cAMP-binding sites on PKA; binding of Rp-cAMPS to PKA prevents the catalytic subunits from being released. PKI peptide, H89, and KT 5720 all act one stage later. After cAMP binding and catalytic subunit release, PKI peptide binds the catalytic subunits and prevents them from phosphorylating targets. (B) H89 and KT 5720 are both competitive antagonists of the ATP sites on the catalytic subunits; without ATP binding, the catalytic subunits are unable to phosphorylate target proteins. C, protein kinase A catalytic subunit; PKI, protein kinase inhibitor peptide; R, protein kinase A regulatory subunit.