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.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Ni Q,Ganesan A,Aye-Han NN,Gao X,Allen MD,Levchenko A,Zhang Jdoi
10.1038/nchembio.478subject
Has Abstractpub_date
2011-01-01 00:00:00pages
34-40issue
1eissn
1552-4450issn
1552-4469pii
nchembio.478journal_volume
7pub_type
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