Guanine nucleotide exchange factors (GEFs) regulate the activity of the small GTP-binding proteins of the Ras superfamily. The Ras family of proteins participate in a diverse array of functions, including signal transduction, cytoskeleton dynamics and intracellular trafficking. Ras proteins cycle between a biologically inactive GDP-bound state and an active GTP-bound state. GEFs catalyze the release of GDP from inactive Ras proteins to enable GTP binding. They include Vav, Vav2, Sos1, Sos2, RCC1, RhoGEF p115, Tiam1, Tiam2, Ral GDS, Ras-GRF1, Ras-GRF2, RasGRP, C3G, FGD1, FGD2, FGD3, NET1, Lbc, Lfc, Lsc, Ost, Frabin, Brx, Dble, Gem and Ect2. Vav has been identified as the specific binding partner of Nef proteins from HIV-1. Coexpression and binding of these partners initiates profound morphological changes, cytoskeletal rearrangements and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication.