Signaling diversity of PKA achieved via a Ca2+-cAMP-PKA oscillatory circuit
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Nature chemical biology - 7(2011), 1 vom: 09. Jan., Seite 34-40 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ni, Qiang [VerfasserIn] |
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| Links: |
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| Themen: |
Calcium |
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| Anmerkungen: |
Date Completed 18.01.2011 Date Revised 16.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/nchembio.478 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM20383769X |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Aye-Han, Nwe-Nwe |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Xinxin |e verfasserin |4 aut | |
| 700 | 1 | |a Allen, Michael D |e verfasserin |4 aut | |
| 700 | 1 | |a Levchenko, Andre |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jin |e verfasserin |4 aut | |
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