The main goal of this proposal is to understand how systems of signaling enzymes work through quantitative studies of Xenopus oocyte maturation. The proposal builds upon recent theoretical studies of the possible kinetic and biochemical properties of signal transduction cascades (linear series of signaling proteins) and loops (signaling systems dominated by feedback) and recent experimental studies of how the Mos/MEK/p42 MAPK and Wee1/Cdc25C/Cdc2 systems do behave in oocytes and oocyte extracts. There are four specific aims: 1. To determine whether hysteresis occurs in the activation of p42 MAPK, and whether it is the biochemical basis for cell fate commitment during oocyte maturation. 2. To determine how switch-like the activation of Cdc2 is during oocyte maturation, and whether any switch-like character is intrinsic to Cdc2 activation or imposed upon it by upstream activators. 3. To determine which components in the MAPK cascade are most sensitive to perturbations, and whether sensitivity trends can be explained and predicted by simple steady-state kinetic considerations. 4. To determine whether regulated nuclear translocation contributes to the ultrasensitive response of p42 MAPK to upstream activators.
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