Molecular and Cellular Dynamics in Mammalian Signal Transduction

PROJECT SUMMARY This MIRA proposal addresses two important avenues of discovery made by our laboratory. In Project 1, we will examine a novel mechanism for allosteric regulation of the MAP kinase, ERK2. This project advances the protein kinase field, by investigating in-depth how protein motions underlie the activation of ERK and how this affects cellular responses to inhibitors of this important enzyme. In Project 2, we will investigate a well-known observation that has never been fully explained, that the responses of cells vary with the strength of ERK signaling. Project 2 advances the signaling field, by discovering and characterizing molecular and cellular events controlled at different thresholds of ERK activity.