Delineation of type I protein kinase A-selective signaling events using an RI anchoring disruptor.

TitleDelineation of type I protein kinase A-selective signaling events using an RI anchoring disruptor.
Publication TypeJournal Article
Year of Publication2006
JournalThe Journal of biological chemistry
Volume281
Issue30
Pagination21535-45
Date Published2006
ISSN0021-9258
Abstract

Control of specificity in cAMP signaling is achieved by A-kinase anchoring proteins (AKAPs), which assemble cAMP effectors such as protein kinase A (PKA) into multiprotein signaling complexes in the cell. AKAPs tether the PKA holoenzymes at subcellular locations to favor the phosphorylation of selected substrates. PKA anchoring is mediated by an amphipathic helix of 14-18 residues on each AKAP that binds to the R subunit dimer of the PKA holoenzymes. Using a combination of bioinformatics and peptide array screening, we have developed a high affinity-binding peptide called RIAD (RI anchoring disruptor) with >1000-fold selectivity for type I PKA over type II PKA. Cell-soluble RIAD selectively uncouples cAMP-mediated inhibition of T cell function and inhibits progesterone synthesis at the mitochondria in steroid-producing cells. This study suggests that these processes are controlled by the type I PKA holoenzyme and that RIAD can be used as a tool to define anchored type I PKA signaling events.

URLhttp://www.jbc.org/cgi/pmidlookup?view=long&pmid=16728392
DOI10.1074/jbc.M603223200
Short TitleJ Biol Chem
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