Figure 7. A Model Based on the Experimentally-Observed Response Functions for Wee1 and Cdc25C Accounts for the Bistability of the Mitotic Trigger.

(A) Experimental data for the hysteretic response of Cdk1 to recombinant Δ65-cyclin B1 in Xenopus egg extracts. Data are taken from a previous publication (Pomerening et al., 2003).

(B) Schematic view of the regulation of cyclin B1-Cdk1 activity by cyclin B1, Wee1A, and Cdc25C. (C) Theoretical steady-state responses based on Equation 6, for five assumed values of k_Wee1A/k_Cdc25C (left to right: 0.125, 0.25, 0.5 (green), 1, 2). (D) Rate-balance plots. The calculated rates of Cdk1 activation (red curves) and inactivation (blue curve) as a function of the concentration of active cyclin B1-Cdk1. The five red curves correspond to five assumed total cyclin concentrations. The ratio k_Wee1A/k_Cdc25C is assumed to be 0.5.

(E) Robustness of the bistable response. For the full model and various modified models, we calculated response curves for 100 randomly-generated parameter sets. The ranges of the parameters were:

• bkgd_Cdc25C = 0 to 0.4 (experimental estimate = 0.2)
  bkgd_Wee1A = 0 to 0.4 (experimental estimate = 0.2)
  EC50_Cdc25C = 20 to 80 nM (experimental estimate = 30 nM)
  EC50_Wee1A = 20 to 80 nM (experimental estimate = 35 nM)
  n_Cdc25C = 5 to 15 (experimental estimate = 11)
  n_Wee1A = 1.5 to 8 (experimental estimate = 3.5)
  k_Wee1A/k_Cdc25C = 0 to 1.5

Random parameter sets were generated and curves were plotted using Mathematica 6.0.3.