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Nat Chem Biol. 2011 Jan;7(1):34-40. doi: 10.1038/nchembio.478. Epub 2010 Nov 21.

Signaling diversity of PKA achieved via a Ca2+-cAMP-PKA oscillatory circuit.

Author information

  • 1Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

Many protein kinases are key nodal signaling molecules that regulate a wide range of cellular functions. These functions may require complex spatiotemporal regulation of kinase activities. Here, we show that protein kinase A (PKA), Ca(2+) and cyclic AMP (cAMP) oscillate in sync in insulin-secreting MIN6 beta cells, forming a highly integrated oscillatory circuit. We found that PKA activity was essential for this oscillatory circuit and was capable of not only initiating the signaling oscillations but also modulating their frequency, thereby diversifying the spatiotemporal control of downstream signaling. Our findings suggest that exquisite temporal control of kinase activity, mediated via signaling circuits resulting from cross-regulation of signaling pathways, can encode diverse inputs into temporal parameters such as oscillation frequency, which in turn contribute to proper regulation of complex cellular functions in a context-dependent manner.

PMID:
21102470
[PubMed - indexed for MEDLINE]
PMCID:
PMC3073414
Free PMC Article

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