GUANINE-NUCLEOTIDE EXCHANGE FACTORS - ACTIVATORS OF THE RAS SUPERFAMILY OF PROTEINS

Ras proteins function as critical relay switches that regulate diverse signaling pathways between cell surface receptors and the nucleus. Ov er the past 2-3 years researchers have identified many components of t hese pathways that mediate Ras activation and effector function. Among these proteins are several guanine nucleotide exchange factors (GEFs) , which are responsible for directly interacting with and activating R as in response to extracellular stimuli. Analogous GEFs regulate Ras-r elated proteins that serve other diverse cellular functions, In partic ular, a growing family of proteins (Dbl homology proteins) has recentl y been identified, which may function as GEFs for the Rho family of Ra s-related proteins. This review summarizes our current knowledge of th e structure, biochemistry and biology of Ras and Rho family GEFs. Addi tionally, we describe mechanisms of GEF activation of Ras in signal tr ansduction and address the potential that deregulated GEFs might contr ibute to malignant transformation through chronic Ras protein activati on.