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Updated: Jun 23, 2026
11:13
Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
Tuning the activation threshold of a kinase network by nested feedback loops.
Quincey A Justman1, Zach Serber, James E Ferrell
1Graduate Group in Biophysics, University of California, San Francisco, CA 94158, USA.
Science (New York, N.Y.)
|April 25, 2009
Summary
Biological systems precisely control responses to signals. This study shows intracellular signaling nodes, like glycogen synthase kinase-3beta (GSK-3beta), can adjust a cell’s response threshold, integrating factors like nutrition to modulate cell fate decisions.
Area of Science:
- Cellular biology
- Biochemistry
- Systems biology
Background:
- Cellular responsiveness to external stimuli is crucial for biological functions.
- Signaling networks integrate diverse inputs to determine cell fate.
- The meiotic entry in Xenopus oocytes is a well-studied model for signal transduction.
Purpose of the Study:
- To investigate how intracellular signaling nodes modulate cellular response thresholds.
- To characterize the role of glycogen synthase kinase-3beta (GSK-3beta) in regulating progesterone responsiveness in Xenopus oocytes.
- To identify additional signals that influence progesterone responsiveness and cell fate decisions.
Main Methods:
- Characterization of the bistable kinase network governing meiotic entry.
- Investigating the feedback mechanisms involving GSK-3beta.
- Identifying and testing the effect of nutritional markers like l-leucine on signaling thresholds.
Main Results:
- GSK-3beta acts as a dampener, raising the progesterone response threshold via a double-negative feedback loop.
- The strength of GSK-3beta signaling directly correlates with the elevated progesterone threshold.
- l-leucine, a nutritional marker, was identified to lower the progesterone threshold, indicating signal integration.
Conclusions:
- Intracellular signaling nodes can actively tune a biological network's response threshold.
- GSK-3beta's feedback loop provides a mechanism to control progesterone responsiveness.
- Oocytes integrate nutritional status with hormonal signals to make critical cell fate decisions, such as meiotic entry.
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