Cyclic adenosine monophosphate (cAMP) is a signal for cellular stress that, in mammalian cells, binds to cAMP-dependent protein kinase (PKA) to activate diverse signaling pathways. Functional diversity is achieved partly by isoform diversity in the catalytic and regulatory (R) subunits of PKA. In particular, there are two main classes of regulatory subunit, type I and type II, that inhibit C in the absence of cAMP. To gain insight into the molecular basis for isoform diversity, Wu et al. have determined the structure of an RIIα holoenzyme and compared it to the previously determined structure of an RIα holoenzyme. The structure shows that the C subunit uses different docking motifs to interact with different inhibitors and shows how ATP differentially regulates the two holoenzymes. The insights may guide design of isoform-specific activators or antagonists for PKA.
- Unraveling PKA Isoform Specificity
The structure of the catalytic subunit of cyclic AMP-dependent protein kinase bound to a regulatory subunit reveals how this enzyme activates two different signaling pathways.Permalink: