The VAV family of signal transduction molecules.
This review summarizes the current knowledge on the structure, expression, and physiological roles of the Vav family, a novel group of signaling transducers with known representatives in mammalian (Vav and Vav-2) and nematodes (Cel Vav). Vav was the first member of this family identified during the course of gene transfer experiments aimed at characterizing loci involved in human neoplasia. This transforming protein displays a complex array of structural motifs, including calponin-homology, acidic, dbl-homology, pleckstrin-homology, cysteine-rich, SH3, and SH2 domains. After activation of cells with extracellular stimuli, Vav becomes phosphorylated on tyrosine residues and catalyzes the exchange of guanosine nucleotides on the GTP-binding protein Rac-1, thereby allowing the transition of this GTPase from the inactive (GDP-loaded) to the active (GTP-loaded) state. In addition, Vav associates with phosphorylated receptors, protein tyrosine kinases, and intracellular phosphoproteins whose identities are now being determined. Gene targeting experiments indicate that vav gene disruption results in severe signaling defects in lymphoid cells, further reinforcing its role as a key regulator of mitogenic pathways. Vav-2 and C. elegans Vav bear significant structural similarity with Vav, suggesting that they will be important players as well in evolutionarily conserved signal transduction pathways involved in mitogenesis and cellular transformation.
Bustelo
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Department of Pathology, School of Medicine and University Hospital, State University of New York at Stony Brook, 11794, USA.
D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D018797:Cell Cycle Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human