Figure 1. A mathematical model of CDK activation recapitulates CDK-cyclin binding preferences observed in vivo.

A model of ordinary differential equations was solved in Virtual Cell ⁴⁹ using the values indicated in the reaction schematic. We modeled accumulation of cyclin A to occur in linear, time-dependent fashion. The intracellular concentrations of Cdk1, Cdk2, and Cdk7 were calculated based on experimentally determined amounts of each CDK per gram of cellular protein ⁴⁵, ⁵⁷, and the kinetic parameters of Cdk2 phosphorylation were derived from experimentally determined values ¹⁰. Models (A) and (B) are identical, except that (B) is modified to allow Cdk1 monomer to be phosphorylated by Cdk7 and dephosphorylated by a phosphatase with kinetics identical to those measured or estimated for Cdk2. The kinetics of phosphorylation of Cdk1 (which occurs only in model B) and Cdk1/cyclin A have not been determined in vitro, so they were assumed to be equivalent to those determined for Cdk2 and Cdk2/cyclin A, respectively. As the values of K_d have not been determined, they were arbitrarily set to 10 nM for those complexes that readily form in vitro (Cdk2/CycA, Cdk2-P/CycA, and Cdk1-P/CycA) and to 10 μM for those that do not (Cdk1/CycA). The kinetic parameters used for CDK monomer dephosphorylation are estimates based on values typical of phosphatases ⁷². We did not include phosphatases acting on CDK/cyclin complexes in the model, because cyclin-binding generally blocks CDK T-loop dephosphorylation ⁴³, ⁴⁴.