Predicted time course of kinase i activity.


Signaling pathways can be a dizzying confusion of interlacing kinases, phosphatases, activators, and inhibitors. But with mathematical models, Reinhart Heinrich (Humboldt-University, Berlin, Germany), Benjamin Neel, and Tom Rapoport (Harvard Medical School, Boston, Massachusetts) have injected some transparency into these murky waters. And they have discovered that phosphatases have more influence than previously thought.

Until now, kinases appeared to be the powerhouses of signal transduction, and phosphatases were almost an afterthought. But when Heinrich derived analytical expressions for steps in an idealized kinase/phosphotase cascade, he found that phosphatases are in control of both the time it takes a signal to travel from the cell surface to its intracellular target and the duration of the signal. Kinases, however, have more influence over the strength of the signal.Although the group started their work using simplified, idealized pathways, the models hold up in more complex pathways, and the outcomes are consistent with the behavior of kinases and phosphatases in vivo. Modeling, says Rapoport, enables scientists to see the relative contributions of a system's components. This information can help to focus future efforts on critical points in a pathway. “My hope is that this paper may stimulate more research on the phosphatases, which must be as tightly regulated as the kinases,” says Rapoport. ▪


Heinrich, R., et al.
Mol. Cell.