期刊
SCIENCE
卷 324, 期 5926, 页码 509-512出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1169498
关键词
-
资金
- NIH [AI49006, GM46383]
- Sandler Family Supporting Foundation
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-3b (GSK-3 beta) as a dampener of progesterone responsiveness. GSK-3 beta 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.
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