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

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.

SUBMITTER: Justman QA

PROVIDER: S-EPMC2880456 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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

Justman Quincey A QA Serber Zach Z Ferrell James E JE El-Samad Hana H Shokat Kevan M KM

Science (New York, N.Y.) 20090401 5926

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 responsive ...[more]

PMID: 19390045

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