17 páginas, 9 figuras.-- El pdf del artículo es la versión de autor.Vav proteins are phosphorylation-dependent GDP/GTP exchange factors for Rho/Rac GTPases. Despite intense characterization of mammalian Vav proteins both biochemically and genetically, there is little information regarding the conservation of their biological properties in lower organisms. To approach this issue, we have performed a characterization of the regulatory, catalytic, and functional properties of the single Vav family member of Drosophila melanogaster. These analyses have shown that the intramolecular mechanisms controlling the enzyme activity of mammalian Vav proteins are already present in Drosophila, suggesting that such properties have been set up before the divergence between protostomes and deuterostomes during evolution. We also show that Drosophila and mammalian Vav proteins have similar catalytic specificities. As a consequence, Drosophila Vav can trigger oncogenic transformation, morphological change, and enhanced cell motility in mammalian cells. Gain-of-function studies using transgenic flies support the implication of this protein in cytoskeletal-dependent processes such as embryonic dorsal closure, myoblast fusion, tracheal development, and the migration/guidance of different cell types. These results highlight the important roles of Vav proteins in the signal transduction pathways regulating cytoskeletal dynamics. Moreover, they indicate that the foundations for the regulatory and enzymatic activities of this protein family have been set up very early during evolution.This work was supported by the US National Cancer Institute (5RO1-CA73735-08 to XRB), the Association for International Cancer Research (00-061 to XRB), the Biomedicine Program of the Spanish Ministry of Education and Science (SAF2003-00028 and BMC2001-2298 to XRB and MDM-B, respectively), and a grant from the Ministry of Education and Culture of the Autonomous Government of Castilla-León (SA051/02 to XRB). J.R.C. is a student of the Molecular and Cellular Cancer Biology graduate program of the CIC and the University of Salamanca who is supported by a FPI fellowship (FP2000-6489) of the Spanish Ministry of Education and Science. M.D.M-B. is a Young Investigator of EMBO. The Centro de Investigación del Cáncer is supported by endowments from the CSIC, University of Salamanca, Castilla- León Autonomous Government, the Spanish Cooperative Network of Cancer Centers (C03/10, Spanish Ministry of Health), and the Foundation for Cancer Research of Salamanca (FICUS).Peer reviewed