Only the combination of a fast and a slow loop provides a quick and reliable reponse.


Findings from Onn Brandman (Stanford University, Stanford, CA) and colleagues suggest that switch-like signal transduction pathways attain speed and reliability by using two positive feedback loops: one fast and one slow.

Just one positive feedback loop is enough to create an all-or-none biological switch. Yet many systems, such as yeast polarization, rely on multiple loops. Removal of the faster loop (GTPase activation) delays polarization, whereas removal of the slower loop (GTPase localization) makes polarization unstable. Using mathematical models, Brandman et al. now show that speed and stability generally require loops of distinct kinetics.

“We can use equations,” says Brandman, “to see what would happen with every combination [of loop kinetics].” One or two fast loops provided a speedy “on” switch, but the system often turned off inappropriately in response to noise. Systems with one or two slow loops, in contrast, remained reliably activated, because short interruptions in a signal were restored before the loop could be shut off. Their slow kinetics, however, created delayed reaction times to the initial incoming signal.

Only the mixture of fast and slow provided both speed and stability. “You can have a switch that is rapidly inducible,” says Brandman. “And if there's enough stimulus, the system will commit to that state.” Systems with kinetically distinct loops include calcium signaling and oocyte maturation, and Brandman expects that many more exist.


Brandman, O., et al.