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Sci. STKE, 16 October 2007
Vol. 2007, Issue 408, p. tw376
[DOI: 10.1126/stke.4082007tw376]


Structural Biology Unraveling PKA Isoform Specificity

Valda J. Vinson

Science, AAAS, Washington, DC 20005, USA

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 RII{alpha} holoenzyme and compared it to the previously determined structure of an RI{alpha} 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.

J. Wu, S. H. J. Brown, S. von Daake, S. S. Taylor, PKA type II{alpha} holoenzyme reveals a combinatorial strategy for isoform diversity. Science 318, 274-279 (2007). [Abstract] [Full Text]

Citation: V. J. Vinson, Unraveling PKA Isoform Specificity. Sci. STKE 2007, tw376 (2007).

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