Enhancing phosphorylation cascades by anomalous diffusion

¹ Experimental Physics I, University of Bayreuth - Universitätsstr. 30, D-95440 Bayreuth, Germany, EU
² Institut für Theoretische Physik - Philosophenweg 19, Universität Heidelberg, D-69120 Heidelberg, Germany, EU

^a matthias.weiss@uni-bayreuth.de

Received: 16 January 2012
Accepted: 8 February 2012

Abstract

A key event in many cellular signaling cascades is the multiple phosphorylation of proteins by specialized kinases. A prototypical example is the mitogen-activated protein kinase (MAPK) that alters the cell's gene transcription after having been phosphorylated twice by the same kinase. Here, we show that anomalous diffusion, induced, for example, by cytoplasmic crowding, can significantly improve the activation of MAPK. Our results on anomalous diffusion with the characteristics of fractional Brownian motion and obstructed diffusion compare favorably to very recent biochemical data on MAPK activation at varying degrees of cytoplasmic crowding. Our results predict any Michaelis-Menten scheme in which a substrate is modified by the same enzyme several times to show an increased performance due to anomalous diffusion when dissociation rates of the intermediate enzyme-substrate complexes are high while the irreversible catalytic step is slow. Thus, crowding-induced anomalous diffusion can strongly alter the behavior of many cellular signaling pathways.