Rab GTPases now comprise a family of >63 members. They are emerging as the key hub element controlling the membrane architecture of eukaryotic cells. They are intimately involved in vesicle targeting and fusion in both the endocytic and exocytic pathways and direct the assembly and disassembly of protein complexes that include regulators (GEFs and GAPs), effectors (tethers/motors) and fusion components (SNAREs) that control membrane targeting and fusion. During the last 3 years the field has virtually exploded with the identification and characterization of many new Rab proteins and their...

The Ras superfamily (>150 human members) encompasses Ras GTPases involved in cell proliferation, Rho GTPases involved in regulating the cytoskeleton, Rab GTPases involved in membrane targeting/fusion and a group of GTPases including Sar1, Arf, Arl and dynamin involved in vesicle budding/fission. These GTPases act as molecular switches and their activities are controlled by a large number of regulatory molecules that affect either GTP loading (guanine nucleotide exchange factors or GEFs) or GTP hydrolysis (GTPase activating proteins or GAPs). In their active state, they interact with a...

Since 1982, Ras proteins have been the subject of intense research investigation by the biomedical research community. The wide interest in Ras has been stimulated for three key reasons.

First, their frequent mutational activation in human cancers establishes Ras proteins as important mediators of oncogenesis and targets for anti-cancer drug discovery. Second, Ras proteins act as signalling nodes activated by diverse extracellular stimuli, and activated Ras in turn regulates a diversity of cytoplasmic signalling networks. Third, Ras proteins are founding members of a large...