proto oncogene proteins c vav


Summary: Proteins that are guanine nucleotide exchange factors for RHO GTPASES. They contain pleckstrin homology and SH2 domains, through which they function as signal transducing adaptor proteins.

Top Publications

  1. Fernandez Zapico M, Gonzalez Paz N, Weiss E, Savoy D, Molina J, Fonseca R, et al. Ectopic expression of VAV1 reveals an unexpected role in pancreatic cancer tumorigenesis. Cancer Cell. 2005;7:39-49 pubmed
    ..Thus, the discovery of prooncogenic pathways regulated by Vav1 makes it an attractive target for therapeutic intervention. ..
  2. Yoo A, Greenwald I. LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans. Science. 2005;310:1330-3 pubmed
    ..Our results suggest that lin-12, mir-61, and vav-1 form a feedback loop that helps maximize lin-12 activity in the presumptive 2 degrees VPCs. ..
  3. Garcia G, Miller R. Age-related changes in lck-Vav signaling pathways in mouse CD4 T cells. Cell Immunol. 2009;259:100-4 pubmed publisher
    ..These changes in lck-Vav signals in resting CD4 cells may contribute in turn to age-related increases in Rac1 activity and declines in phosphorylation of cytoskeletal proteins including Ezrin and Moesin. ..
  4. Malhotra S, Kovats S, Zhang W, Coggeshall K. Vav and Rac activation in B cell antigen receptor endocytosis involves Vav recruitment to the adapter protein LAB. J Biol Chem. 2009;284:36202-12 pubmed publisher
    ..This is the first description of a sequential signal transduction pathway from BCR to internalization and antigen presentation. ..
  5. Henderson R, Grys K, Vehlow A, de Bettignies C, Zachacz A, Henley T, et al. A novel Rac-dependent checkpoint in B cell development controls entry into the splenic white pulp and cell survival. J Exp Med. 2010;207:837-53 pubmed publisher
    ..Thus, these studies identify a novel developmental checkpoint that coincides with B cell positive selection. ..
  6. Yi F, Xia M, Li N, Zhang C, Tang L, Li P. Contribution of guanine nucleotide exchange factor Vav2 to hyperhomocysteinemic glomerulosclerosis in rats. Hypertension. 2009;53:90-6 pubmed publisher
    ..We concluded that Vav2-mediated activation of NADPH oxidase is an important initiating mechanism resulting in hyperhomocysteinemic glomerular injury through enhanced local oxidative stress. ..
  7. Moon M, Gomez T. Balanced Vav2 GEF activity regulates neurite outgrowth and branching in vitro and in vivo. Mol Cell Neurosci. 2010;44:118-28 pubmed publisher
    ..Together, we suggest that balanced Vav2 activity is necessary for optimal neurite outgrowth and promotes branching by targeting GEF activity to branch points. ..
  8. Reeve J, Zou W, Liu Y, Maltzman J, Ross F, Teitelbaum S. SLP-76 couples Syk to the osteoclast cytoskeleton. J Immunol. 2009;183:1804-12 pubmed publisher
    ..Finally, c-Fms-activated Syk also exerts its OC cytoskeleton-organizing effect in a SLP-76/Vav3-dependent manner. ..
  9. Bertagnolo V, Grassilli S, D Aguanno S, Brugnoli F, Bavelloni A, Faenza I, et al. Mass spectrometry-based identification of Y745 of Vav1 as a tyrosine residue crucial in maturation of acute promyelocytic leukemia-derived cells. J Proteome Res. 2010;9:752-60 pubmed publisher

More Information


  1. Mortensen M, Ferguson D, Edelmann M, Kessler B, Morten K, Komatsu M, et al. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc Natl Acad Sci U S A. 2010;107:832-7 pubmed publisher
    ..In summary, we show that the selective removal of mitochondria by autophagy, but not other organelles, during erythropoeisis is essential and that this is a necessary developmental step in erythroid cells...
  2. Oakley F, Smith R, Engelhardt J. Lipid rafts and caveolin-1 coordinate interleukin-1beta (IL-1beta)-dependent activation of NFkappaB by controlling endocytosis of Nox2 and IL-1beta receptor 1 from the plasma membrane. J Biol Chem. 2009;284:33255-64 pubmed publisher
    ..Our results fill in an important mechanistic gap in the understanding of early IL-1R1 and Nox2 signaling events that control NFkappaB activation, a redox-dependent process important in inflammation. ..
  3. Chang J, Koike T, Iwashima M. hnRNP-K is a nuclear target of TCR-activated ERK and required for T-cell late activation. Int Immunol. 2009;21:1351-61 pubmed publisher
    ..Since Vav1 is an essential molecule for T-cell activation, the data suggest that ERK signaling is required for T-cell activation partly by inhibiting activation-induced proteolysis of Vav1. ..
  4. Sauzeau V, Sevilla M, Montero M, Bustelo X. The Rho/Rac exchange factor Vav2 controls nitric oxide-dependent responses in mouse vascular smooth muscle cells. J Clin Invest. 2010;120:315-30 pubmed publisher
  5. Lazer G, Idelchuk Y, Schapira V, Pikarsky E, Katzav S. The haematopoietic specific signal transducer Vav1 is aberrantly expressed in lung cancer and plays a role in tumourigenesis. J Pathol. 2009;219:25-34 pubmed publisher
    ..These data suggest that Vav1 plays a role in the neoplastic process in lung cancer, identifying it as a potential therapeutic target for lung cancer therapy. ..
  6. Phillipson M, Heit B, Parsons S, Petri B, Mullaly S, Colarusso P, et al. Vav1 is essential for mechanotactic crawling and migration of neutrophils out of the inflamed microvasculature. J Immunol. 2009;182:6870-8 pubmed publisher
    ..Clearly, Vav1 is critical for the complex interplay between LFA-1 and Mac-1 that underlies the programmed intravascular crawling of neutrophils. ..
  7. Quevedo C, Sauzeau V, Menacho Márquez M, Castro Castro A, Bustelo X. Vav3-deficient mice exhibit a transient delay in cerebellar development. Mol Biol Cell. 2010;21:1125-39 pubmed publisher
    ..These results indicate that Vav3 function contributes to the timely developmental progression of the cerebellum. ..
  8. Malartre M, Ayaz D, Amador F, Martín Bermudo M. The guanine exchange factor vav controls axon growth and guidance during Drosophila development. J Neurosci. 2010;30:2257-67 pubmed publisher
    ..Thus, we propose that vav acts in coordination with other GEFs to regulate axon growth and guidance during development by linking guidance signals to the cytoskeleton via the modulation of Rac activity. ..
  9. Chauveau A, Aucher A, Eissmann P, Vivier E, Davis D. Membrane nanotubes facilitate long-distance interactions between natural killer cells and target cells. Proc Natl Acad Sci U S A. 2010;107:5545-50 pubmed publisher
    ..Finally, target cells that remained connected to an NK cell by a nanotube were frequently lysed, whereas removing the nanotube using a micromanipulator reduced lysis of these target cells...
  10. Rolli Derkinderen M, Toumaniantz G, Pacaud P, Loirand G. RhoA phosphorylation induces Rac1 release from guanine dissociation inhibitor alpha and stimulation of vascular smooth muscle cell migration. Mol Cell Biol. 2010;30:4786-96 pubmed publisher
    ..These results suggest that the phosphorylation of RhoA represents a novel potent and physiological GDI? displacement factor that leads to Rac1 activation and regulation of Rac1-dependent VSMC functions. ..
  11. Haubert D, Weckbecker G. Vav1 couples the T cell receptor to cAMP response element activation via a PKC-dependent pathway. Cell Signal. 2010;22:944-54 pubmed publisher
    ..We identify Vav1 as an essential component of TCR-induced CRE activation and gene expression, which underlines the central role for Vav1 as key player for TCR signal transduction and gene expression. ..
  12. García Bernal D, Parmo Cabañas M, Dios Esponera A, Samaniego R, Hernán P de la Ossa D, Teixido J. Chemokine-induced Zap70 kinase-mediated dissociation of the Vav1-talin complex activates alpha4beta1 integrin for T cell adhesion. Immunity. 2009;31:953-64 pubmed publisher
    ..Our data suggest that Vav1 might function as a repressive adaptor of talin that must dissociate from alpha4beta1-talin complexes for efficient integrin activation. ..
  13. Kasirer Friede A, Ruggeri Z, Shattil S. Role for ADAP in shear flow-induced platelet mechanotransduction. Blood. 2010;115:2274-82 pubmed publisher
    ..These results establish that ADAP is an essential component of alphaIIbbeta3-mediated platelet mechanotransduction that promotes F-actin assembly and enables platelet spreading and thrombus stabilization under fluid shear stress. ..
  14. Nischwitz S, Cepok S, Kroner A, Wolf C, Knop M, Müller Sarnowski F, et al. Evidence for VAV2 and ZNF433 as susceptibility genes for multiple sclerosis. J Neuroimmunol. 2010;227:162-6 pubmed publisher
    ..No SNPs outside the HLA region reached a genome wide level of significance. Nevertheless, we found suggestive evidence for an association of MS with variants in two new genes, the VAV2 gene and the gene for ZNF433. ..
  15. Ruiz S, Santos E, Bustelo X. The use of knockout mice reveals a synergistic role of the Vav1 and Rasgrf2 gene deficiencies in lymphomagenesis and metastasis. PLoS ONE. 2009;4:e8229 pubmed publisher
    ..They also suggest that the inactivation of Vav1 function may represent an inadequate strategy to treat T-cell lymphomas, especially those associated with low levels of Rasgrf2 gene expression. ..
  16. Li R, Wei F, Yu J, Li H, Ren X, Hao X. IDO inhibits T-cell function through suppressing Vav1 expression and activation. Cancer Biol Ther. 2009;8:1402-8 pubmed
    ..These studies provide insight into understanding the mechanisms of immune escape induced by IDO and therapeutic application of IDO inhibitors for cancer treatment. ..
  17. Kim H, Choi H, Shin J, Kim K, Huh J, Lee S, et al. Selective inhibition of RANK blocks osteoclast maturation and function and prevents bone loss in mice. J Clin Invest. 2009;119:813-25 pubmed publisher
    ..These data may be useful in the development of selective therapeutic agents for the treatment of osteoporosis and other bone diseases. ..
  18. Gan T, Jude C, Zaffuto K, Ernst P. Developmentally induced Mll1 loss reveals defects in postnatal haematopoiesis. Leukemia. 2010;24:1732-41 pubmed publisher
    ..Collectively, these data support the conclusion that Mll has an essential role in sustaining postnatal haematopoiesis. ..
  19. Barda Saad M, Shirasu N, Pauker M, Hassan N, Perl O, Balbo A, et al. Cooperative interactions at the SLP-76 complex are critical for actin polymerization. EMBO J. 2010;29:2315-28 pubmed publisher
    ..Disruption of the VAV1:Nck interaction deleteriously affected actin polymerization. These novel findings shed new light on the mechanism of actin polymerization after T-cell activation. ..
  20. Fraser H, Dendrou C, Healy B, Rainbow D, Howlett S, Smink L, et al. Nonobese diabetic congenic strain analysis of autoimmune diabetes reveals genetic complexity of the Idd18 locus and identifies Vav3 as a candidate gene. J Immunol. 2010;184:5075-84 pubmed publisher
    ..This study also demonstrates that a congenic strain mapping approach can isolate closely linked susceptibility genes. ..
  21. Shen M, Yen A. c-Cbl tyrosine kinase-binding domain mutant G306E abolishes the interaction of c-Cbl with CD38 and fails to promote retinoic acid-induced cell differentiation and G0 arrest. J Biol Chem. 2009;284:25664-77 pubmed publisher
    ..The results demonstrate the importance of the Gly306 residue in the ability of c-Cbl to propel RA-induced differentiation. ..
  22. Krishnan S, Juang Y, Chowdhury B, Magilavy A, Fisher C, Nguyen H, et al. Differential expression and molecular associations of Syk in systemic lupus erythematosus T cells. J Immunol. 2008;181:8145-52 pubmed
    ..Thus, we propose molecular targeting of Syk as a measure to control abnormal T cell responses in SLE. ..
  23. Del Valle Pérez B, Martínez V, Lacasa Salavert C, Figueras A, Shapiro S, Takafuta T, et al. Filamin B plays a key role in vascular endothelial growth factor-induced endothelial cell motility through its interaction with Rac-1 and Vav-2. J Biol Chem. 2010;285:10748-60 pubmed publisher
    ..In conclusion, our results reveal a crucial role for FLNB in endothelial cell migration and in the angiogenic process in adult endothelial cells. ..
  24. He M, Liu H, Turner M, Taussig M. Detection of protein-protein interactions by ribosome display and protein in situ immobilisation. N Biotechnol. 2009;26:277-81 pubmed publisher
    ..The method has promise for library screening of pairwise protein interactions, down to the analytical level of individual domain or motif mapping...
  25. Daubon T, Chasseriau J, El Ali A, Rivet J, Kitzis A, Constantin B, et al. Differential motility of p190bcr-abl- and p210bcr-abl-expressing cells: respective roles of Vav and Bcr-Abl GEFs. Oncogene. 2008;27:2673-85 pubmed
    ..These results suggest that Rac1 activation by Vav triggers the motility of Bcr-Abl-expressing Ba/F3 cells, while the specific amoeboid mode of motility induced by p210(bcr-abl) is a consequence of RhoA activation. ..
  26. Peirce M, Brook M, Morrice N, Snelgrove R, Begum S, Lanfrancotti A, et al. Themis2/ICB1 is a signaling scaffold that selectively regulates macrophage Toll-like receptor signaling and cytokine production. PLoS ONE. 2010;5:e11465 pubmed publisher
    ..We hypothesise that Themis2 may constitute a novel, physiological control point in macrophage inflammatory responses. ..
  27. Holthusen K, Gonzalez A, Meneses P. Guanine exchange factor Vav2: a novel potential target for the development of drugs effective in the prevention of papillomavirus infection and disease. Am J Ther. 2009;16:496-507 pubmed publisher
    ..Our data propose the Vav2-related pathway as a potential therapeutic target for papillomavirus infection and oncogenic development as has been shown for breast cancer invasiveness. ..
  28. Brugnoli F, Lambertini E, Varin Blank N, Piva R, Marchisio M, Grassilli S, et al. Vav1 and PU.1 are recruited to the CD11b promoter in APL-derived promyelocytes: role of Vav1 in modulating PU.1-containing complexes during ATRA-induced differentiation. Exp Cell Res. 2010;316:38-47 pubmed publisher
    ..1 to its consensus sequence on the CD11b promoter and, ultimately, in regulating CD11b expression during the late stages of neutrophil differentiation of APL-derived promyelocytes. ..
  29. Spurrell D, Luckashenak N, Minney D, Chaplin A, Penninger J, Liwski R, et al. Vav1 regulates the migration and adhesion of dendritic cells. J Immunol. 2009;183:310-8 pubmed publisher
    ..However, there was less inhibition in the absence of Vav1. These findings suggest that DC migration is negatively regulated by adhesion and integrin-mediated signaling and that Vav1 has a central role in this process. ..
  30. Graham D, Akilesh H, Gmyrek G, Piccio L, Gilfillan S, Sim J, et al. ITAM signaling in dendritic cells controls T helper cell priming by regulating MHC class II recycling. Blood. 2010;116:3208-18 pubmed publisher
    ..We propose a novel mechanism for control of T helper cell priming. ..
  31. Gao C, Blystone S. A Pyk2-Vav1 complex is recruited to beta3-adhesion sites to initiate Rho activation. Biochem J. 2009;420:49-56 pubmed publisher
    ..These results indicate that Pyk2 is a critical signalling molecule downstream of beta3 integrin tyrosine phosphorylation and mediates Vav1 recruitment to accomplish actin reorganization necessary for adhesion. ..
  32. Cremasco V, Graham D, Novack D, Swat W, Faccio R. Vav/Phospholipase Cgamma2-mediated control of a neutrophil-dependent murine model of rheumatoid arthritis. Arthritis Rheum. 2008;58:2712-22 pubmed publisher
    ..This study identifies a Vav/PLCgamma2-dependent signaling pathway as a possible therapeutic target for the treatment of inflammation and bone disruption in arthritis. ..
  33. Bhavsar P, Vigorito E, Turner M, Ridley A. Vav GEFs regulate macrophage morphology and adhesion-induced Rac and Rho activation. Exp Cell Res. 2009;315:3345-58 pubmed publisher
  34. Jagodic M, Colacios C, Nohra R, Dejean A, Beyeen A, Khademi M, et al. A role for VAV1 in experimental autoimmune encephalomyelitis and multiple sclerosis. Sci Transl Med. 2009;1:10ra21 pubmed publisher
    ..We conclude that VAV1 plays a central role in controlling central nervous system immune-mediated disease and proinflammatory cytokine production critical for disease pathogenesis. ..
  35. Malhotra S, Kovats S, Zhang W, Coggeshall K. B cell antigen receptor endocytosis and antigen presentation to T cells require Vav and dynamin. J Biol Chem. 2009;284:24088-97 pubmed publisher
    ..This is the first demonstration of a link between Vav and Rac in BCR internalization leading to antigen presentation to T cells. ..
  36. Gonzalez Murillo A, Lozano M, Alvarez L, Jacome A, Almarza E, Navarro S, et al. Development of lentiviral vectors with optimized transcriptional activity for the gene therapy of patients with Fanconi anemia. Hum Gene Ther. 2010;21:623-30 pubmed publisher
    ..On the basis of the efficacy and safety properties of PGK LVs, a PGK LV carrying FANCA and a mutant WPRE is proposed as an optimized vector for the gene therapy of patients with FA-A. ..
  37. Afshari F, Kwok J, Fawcett J. Astrocyte-produced ephrins inhibit schwann cell migration via VAV2 signaling. J Neurosci. 2010;30:4246-55 pubmed publisher
    ..Overall, we suggest that Eph/ephrin interactions inhibit Schwann cell migration and intermingling with astrocytes via VAV signaling affecting integrin function. ..
  38. Toumaniantz G, Ferland McCollough D, Cario Toumaniantz C, Pacaud P, Loirand G. The Rho protein exchange factor Vav3 regulates vascular smooth muscle cell proliferation and migration. Cardiovasc Res. 2010;86:131-40 pubmed publisher
  39. Ishida M, Itsukaichi T, Kobayashi D, Kikuchi H. Alteration of the PKC theta-Vav1 complex and phosphorylation of Vav1 in TCDD-induced apoptosis in the lymphoblastic T cell line, L-MAT. Toxicology. 2010;275:72-8 pubmed publisher
    ..Finally, PKC theta may mediate the transfer of the apoptotic signal to downstream components. ..
  40. Loss L, Sadanandam A, Durinck S, Nautiyal S, Flaucher D, Carlton V, et al. Prediction of epigenetically regulated genes in breast cancer cell lines. BMC Bioinformatics. 2010;11:305 pubmed publisher
    ..Subnetwork enrichment of these predicted markers further suggests that epigenetic regulation of individual genes occurs in a coordinated fashion and through common regulators. ..
  41. Lazer G, Pe er L, Farago M, Machida K, Mayer B, Katzav S. Tyrosine residues at the carboxyl terminus of Vav1 play an important role in regulation of its biological activity. J Biol Chem. 2010;285:23075-85 pubmed publisher
    ..The association of Vav1 with other proteins, detected by SH2 profiling, might affect other Vav1-dependent activities, such as NFAT stimulation...
  42. Liu Y, Wu X, Dong Z, Lu S. The molecular mechanism of Vav3 oncogene on upregulation of androgen receptor activity in prostate cancer cells. Int J Oncol. 2010;36:623-33 pubmed
  43. Sindrilaru A, Peters T, Schymeinsky J, Oreshkova T, Wang H, Gompf A, et al. Wound healing defect of Vav3-/- mice due to impaired {beta}2-integrin-dependent macrophage phagocytosis of apoptotic neutrophils. Blood. 2009;113:5266-76 pubmed publisher
  44. Fernandez Salguero P. A remarkable new target gene for the dioxin receptor: The Vav3 proto-oncogene links AhR to adhesion and migration. Cell Adh Migr. 2010;4:172-5 pubmed
  45. Mori M, Murata Y, Kotani T, Kusakari S, Ohnishi H, Saito Y, et al. Promotion of cell spreading and migration by vascular endothelial-protein tyrosine phosphatase (VE-PTP) in cooperation with integrins. J Cell Physiol. 2010;224:195-204 pubmed publisher
    ..These results suggest that VE-PTP, in cooperation with integrins, regulates the spreading and migration of endothelial cells during angiogenesis. ..
  46. Fadda L, Borhis G, Ahmed P, Cheent K, Pageon S, Cazaly A, et al. Peptide antagonism as a mechanism for NK cell activation. Proc Natl Acad Sci U S A. 2010;107:10160-5 pubmed publisher
    ..Our data show that, as for T cells, small changes in the peptide content of MHC class I can regulate NK cell activity. ..
  47. David R, Ma L, Ivetic A, Takesono A, Ridley A, Chai J, et al. T-cell receptor- and CD28-induced Vav1 activity is required for the accumulation of primed T cells into antigenic tissue. Blood. 2009;113:3696-705 pubmed publisher
    ..This novel function of APC-induced, and TCR- and CD28-mediated Vav1 activity in the regulation of effector T-cell immunity highlights its potential as a therapeutic target in T cell-mediated tissue damage. ..
  48. Kim H, Das A, Gross C, Bryceson Y, Long E. Synergistic signals for natural cytotoxicity are required to overcome inhibition by c-Cbl ubiquitin ligase. Immunity. 2010;32:175-86 pubmed publisher
    ..Therefore, NK cell activation by synergizing receptors is regulated at the level of Vav1 by a hierarchy of inhibitory mechanisms. ..
  49. Hollmann A, Aloyz R, Baker K, Dirnhofer S, Owens T, Sladek R, et al. Vav-1 expression correlates with NF?B activation and CD40-mediated cell death in diffuse large B-cell lymphoma cell lines. Hematol Oncol. 2010;28:142-50 pubmed publisher
    ..Our results suggest that Vav-1 expression may be associated with activated B-cell DLBCL origin and higher proliferative activity, and indicate Vav-1 as a potential marker to identify tumours likely to respond to CD40-targeted therapies. ..
  50. Fujikawa K, Iwata T, Inoue K, Akahori M, Kadotani H, Fukaya M, et al. VAV2 and VAV3 as candidate disease genes for spontaneous glaucoma in mice and humans. PLoS ONE. 2010;5:e9050 pubmed publisher
  51. Thalappilly S, Soubeyran P, Iovanna J, Dusetti N. VAV2 regulates epidermal growth factor receptor endocytosis and degradation. Oncogene. 2010;29:2528-39 pubmed publisher
    ..Thus, in this work, we report for the first time that Vav2 can regulate growth factors receptor signalling by slowing receptor internalization and degradation through its interaction with endosome-associated proteins. ..
  52. Chang Y, Tien S, Tien H, Zhang H, Bokoch G, Chang Z. p210(Bcr-Abl) desensitizes Cdc42 GTPase signaling for SDF-1alpha-directed migration in chronic myeloid leukemia cells. Oncogene. 2009;28:4105-15 pubmed publisher
  53. Brantley Sieders D, Zhuang G, Vaught D, Freeman T, Hwang Y, Hicks D, et al. Host deficiency in Vav2/3 guanine nucleotide exchange factors impairs tumor growth, survival, and angiogenesis in vivo. Mol Cancer Res. 2009;7:615-23 pubmed publisher
    ..These data suggest that Vav2/3 guanine nucleotide exchange factors play a critical role in host-mediated tumor progression and angiogenesis, particularly in tumor endothelium. ..