EMERGING CONCEPTS IN THE RAS SUPERFAMILY OF GTP-BINDING PROTEINS

The Ras superfamily of GTP-binding proteins (> 50 members) regulates a diverse spectrum of intracellular processes. These include cellular proliferation and differentiation, intracellular vesicular trafficking, cytoskeletal control, NADPH oxidase function, as well as others. In this review, we describe recent progress and emerging themes in the action and regulation of these important cellular regulatory molecules. Structural studies have provided insight into the function of low molecular weight GTP-binding proteins (LMWGs) as molecular switches, and are defining modes of interaction with associated regulatory molecules. Details of the enzymatic processes involved in the posttranslational processing of LMWGs, and how this processing is important for protein function, are being elucidated. A variety of GTPase activating proteins, GDP/GTP dissociation stimulators, and GDP dissociation inhibitors have been identified, and their ability to determine the activity of LMWG-regulated systems is being worked out. The discovery of multifunctional regulatory molecules has indicated that substantial ''crosstalk'' between various LMWG may occur. The continuing emergence of additional cellular functions that are regulated by LMWGs, and particularly the recent availability of in vitro analytical systems for studies of the mechanism (or mechanisms) of action of LMWGs, is resulting in a wealth of information about the regulation and integration of cellular signaling, form, and function.