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Science. 2009 Apr 24;324(5926):509-12. doi: 10.1126/science.1169498.

Tuning the activation threshold of a kinase network by nested feedback loops.

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  • 1Graduate Group in Biophysics, University of California, San Francisco, CA 94158, USA.

Abstract

Determining proper responsiveness to incoming signals is fundamental to all biological systems. We demonstrate that intracellular signaling nodes can tune a signaling network's response threshold away from the basal median effective concentration established by ligand-receptor interactions. Focusing on the bistable kinase network that governs progesterone-induced meiotic entry in Xenopus oocytes, we characterized glycogen synthase kinase-3beta (GSK-3beta) as a dampener of progesterone responsiveness. GSK-3beta engages the meiotic kinase network through a double-negative feedback loop; this specific feedback architecture raises the progesterone threshold in correspondence with the strength of double-negative signaling. We also identified a marker of nutritional status, l-leucine, which lowers the progesterone threshold, indicating that oocytes integrate additional signals into their cell-fate decisions by modulating progesterone responsiveness.

PMID:
19390045
PMCID:
PMC2880456
DOI:
10.1126/science.1169498
[PubMed - indexed for MEDLINE]
Free PMC Article
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