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

Qiang Ni, Ambhighainath Ganesan, Nwe Nwe Aye-Han, Xinxin Gao, Michael D. Allen, Andre Levchenko, Jin Zhang

Research output: Contribution to journalArticle

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), Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)34-40
Number of pages7
JournalNature chemical biology
Volume7
Issue number1
DOIs
StatePublished - Jan 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Ni, Q., Ganesan, A., Aye-Han, N. N., Gao, X., Allen, M. D., Levchenko, A., & Zhang, J. (2011). Signaling diversity of PKA achieved via a Ca2+ -cAMP-PKA oscillatory circuit. Nature chemical biology, 7(1), 34-40. https://doi.org/10.1038/nchembio.478