ABSTRACT
ras-p21 proteins cycle between inactive and active states. 2 , 3 Conversion of the inactive, GDP-bound form to the active, GTP-bound form is mediated by proteins referred to as “exchange factors”, “guanine-nucleotide releasing factors” or GDP dissociation stimulators (GDSs). Conversion of the active state to the inactive state is mediated by GTPase-activating proteins (GAPs). The level of active ras-p21 in cells is determined by the balance between exchange activity and GAP activity. Clearly, if these two activities were equal, ras-p21-GDP and ras-p21-GTP would exist in equal proportions. However, in most cells, the GDP form predominates 6 , 10 , 11 , 20 , 24 indicating that GAP activity exceeds exchange activity. This situation changes in activated cells, in which the GTP form accumulates. In this chapter, we will discuss ways in which these changes in GDP/GTP could be regulated, and the possible significance of this regulation. Elsewhere in this volume, the possible role of membrane localization and processing in ras-p21 will be discussed (Chapter 3).
