Oscillatory dynamics in the mitogen-activated protein kinase cascade

Abstract

We have used quantitative modeling of signaling networks to show that the mitogen-activated protein kinase cascade - a highly conserved signaling network in eukaryotes - can functions as a low-pass filter by amplifying low-frequency oscillations and attenuating high-frequency oscillations. This filtering function of the kinase cascade is in addition to other known functions such as being an ultrasensitive switch. We show how this low-pass filtering regulates downstream cellular functions and cellular physiology. We also show how the presence of scaffold proteins in the kinase cascade modifies the properties of the low-pass filter. In particular, we find that the presence of scaffold proteins destroys the properties of the low-pass filtering, and instead attenuate all oscillations. In particular, the higher the scaffold concentration, the greater the attenuation.