Biophysical Characterization of the Ras Protein

Abstract

Ras is a central switch in regulation of cell proliferation and differentiation. It becomes activated by extracellular stimuli like growth factors and relays the signal into diverse cellular pathways. A balanced action of regulatory proteins is required to maintain the desired level of Ras activity. Oncogenic mutations in Ras lead to uncontrollable over-function, resulting in transformation of the cell. Therefore Ras became a target in many searches for anti-cancer agents. From the biochemical point of view Ras serves as the paradigm of the superfamily of GTP-binding proteins which fulfill cellular functions as diverse as transmission of vision and regulation of cell morphology. The common theme is switching between the GTP- and GDP-bound forms which correspond to the active and silent states, respectively. This article describes the function of Ras on the molecular level, leaving the enormous wealth of biological data in the Ras field largely aside. Rather, the focus is put on biochemical and biophysical methods which were used to analyze the interactions with the diverse partner molecules in a quantitative way to elucidate the mechanism of activation and regulation.