Rab GTPases are key regulators of membrane traffic pathways within eukaryotic cells. They are specifically activated by guanine nucleotide exchange factors (GEFs), which convert them from their "inactive" GDP-bound form to the "active" GTP-bound form. In higher eukaryotes, proteins containing DENN-domains comprise a major GEF family. Here we describe at 2.1-Å resolution the first structure of a...

Rab family small GTPases function as molecular switches in the regulation of membrane traffic, and their activity is thought to be controlled by guanine nucleotide exchange factors (GEFs). However, the role of GEFs in targeting Rab proteins to specific membrane compartments is poorly understood. We have recently reported finding that Rabex-5, originally described as a Rab5-GEF, also functions a...

The Vav family of proteins are guanine nucleotide exchange factors (GEFs) for the Rho family of GTPases, which regulate various cellular functions, including T-cell activation. They contain a catalytic Dbl homology (DH) domain that is invariably followed by a pleckstrin homology (PH) domain, which is often required for catalytic activity. Vav proteins are the first GEFs for which an additional ...

A variety of cellular processes rely on G-proteins, which cycle through active GTP-bound and inactive GDP-bound forms. The switch between these states is commonly regulated by GEFs (guanine-nucleotide-exchange factors) and GAPs (GTPase-activating proteins). Although G-proteins have structural similarity, GEFs are very diverse proteins. A complex example of this system is seen in eukaryotic tran...

The regulators of the Rho-family GTPases, GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs), play important roles in axon guidance. By means of a functional genomic study of the Rho-family GEFs and GAPs in Drosophila, we have identified a Rho-family GAP, CrossGAP (CrGAP), which is involved in Roundabout (Robo) receptor-mediated repulsive axon guidance. CrGAP physically assoc...

Over the past decade, an increasing appreciation has developed for the role of small GTP-binding proteins (GTPases) as critical molecular switches. Small GTPases function as important regulators of multiple cellular processes by transducing signals from extracellular stimuli to intracellular effector pathways. The three primary members of the Rho family of GTPases include Rho, Rac, and Cdc42, w...