Genomes and Genes
Gene Symbol: Vav2
Description: vav 2 oncogene
Alias: 2810040F13Rik, AI847175, Vav-2, guanine nucleotide exchange factor VAV2
- Chang K, Sanchez Aguilera A, Shen S, Sengupta A, Madhu M, Ficker A, et al. Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation, and survival. Blood. 2012;120:800-11 pubmed publisher..Compensatory up-regulation of expression and activation of Vav3 in Vav1/Vav2-deficient B-cell progenitors increases the transformation ability of p190-BCR-ABL...
- Pearce A, Senis Y, Billadeau D, Turner M, Watson S, Vigorito E. Vav1 and vav3 have critical but redundant roles in mediating platelet activation by collagen. J Biol Chem. 2004;279:53955-62 pubmed..Vav1, Vav2, and Vav3 play a crucial role in the regulation of phospholipase C gamma (PLC gamma) isoforms by immuno-tyrosine-..
- Weber M, Treanor B, Depoil D, Shinohara H, Harwood N, Hikida M, et al. Phospholipase C-gamma2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen. J Exp Med. 2008;205:853-68 pubmed publisher..Thus, we demonstrate the importance of cooperation between components of the microsignalosome in the amplification of signaling and propagation of B cell spreading, which is critical for appropriate B cell activation. ..
- Lawson C, Donald S, Anderson K, Patton D, Welch H. P-Rex1 and Vav1 cooperate in the regulation of formyl-methionyl-leucyl-phenylalanine-dependent neutrophil responses. J Immunol. 2011;186:1467-76 pubmed publisher..We conclude that P-Rex1 and Vav1 together are the major fMLFR-dependent Dbl family Rac-GEFs in neutrophils and cooperate in the control of fMLF-stimulated neutrophil responses. ..
- Hunter S, Zhuang G, Brantley Sieders D, Swat W, Cowan C, Chen J. Essential role of Vav family guanine nucleotide exchange factors in EphA receptor-mediated angiogenesis. Mol Cell Biol. 2006;26:4830-42 pubmed..Here we report the identification of Vav2 and Vav3 as guanine nucleotide exchange factors (GEFs) that link the EphA2 receptor to Rho family GTPase activation ..
- Hall A, Gakidis M, Glogauer M, Wilsbacher J, Gao S, Swat W, et al. Requirements for Vav guanine nucleotide exchange factors and Rho GTPases in FcgammaR- and complement-mediated phagocytosis. Immunity. 2006;24:305-16 pubmed..In contrast, Vav is specifically required for complement-mediated phagocytosis, suggesting that Rac is regulated by GEFs other than Vav downstream of the FcgammaR. ..
- Cella M, Fujikawa K, Tassi I, Kim S, Latinis K, Nishi S, et al. Differential requirements for Vav proteins in DAP10- and ITAM-mediated NK cell cytotoxicity. J Exp Med. 2004;200:817-23 pubmed..It is also possible that two other Vav family molecules, Vav2 and Vav3, are involved in NK cell activation...
- Miletic A, Graham D, Montgrain V, Fujikawa K, Kloeppel T, Brim K, et al. Vav proteins control MyD88-dependent oxidative burst. Blood. 2007;109:3360-8 pubmed..of LPS-induced MyD88-dependent activation of Rac2, NADPH oxidase, and ROI production using mice deficient in Vav1, Vav2, and Vav3...
- Doody G, Bell S, Vigorito E, Clayton E, McAdam S, Tooze R, et al. Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation. Nat Immunol. 2001;2:542-7 pubmed..B cells from Vav-1(-/-)Vav-2(-/-) mice respond poorly to antigen receptor triggering, both in terms of proliferation and calcium release. These studies show the importance of Vav-2 in humoral immune responses and B cell maturation. ..
- Tedford K, Nitschke L, Girkontaite I, Charlesworth A, Chan G, Sakk V, et al. Compensation between Vav-1 and Vav-2 in B cell development and antigen receptor signaling. Nat Immunol. 2001;2:548-55 pubmed..These findings establish a role for Vav-2 in BCR calcium signaling and reveal that the Vav family of GEFs is critical to B cell development and function. ..
- Sauzeau V, Carvajal Gonzalez J, Riolobos A, Sevilla M, Menacho Márquez M, Román A, et al. Transcriptional factor aryl hydrocarbon receptor (Ahr) controls cardiovascular and respiratory functions by regulating the expression of the Vav3 proto-oncogene. J Biol Chem. 2011;286:2896-909 pubmed publisher..Our data also reveal the presence of sympathoexcitation and new cardiorespiratory defects in Ahr(-/-) mice. ..
- Pearce A, McCarty O, Calaminus S, Vigorito E, Turner M, Watson S. Vav family proteins are required for optimal regulation of PLCgamma2 by integrin alphaIIbbeta3. Biochem J. 2007;401:753-61 pubmed..These results demonstrate that Vav1 and Vav3 are required for optimal spreading and regulation of PLCgamma2 by integrin alphaIIbbeta3, but that their requirement is by-passed upon G-protein receptor activation. ..
- Arana E, Vehlow A, Harwood N, Vigorito E, Henderson R, Turner M, et al. Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation. Immunity. 2008;28:88-99 pubmed publisher..and Rac2, were activated rapidly downstream of Src-family kinases, guanine-nucleotide exchange factors Vav1 and Vav2, and phosphoinositide-3 kinase (PI3K) after BCR engagement...
- Graham D, Stephenson L, Lam S, Brim K, Lee H, Bautista J, et al. An ITAM-signaling pathway controls cross-presentation of particulate but not soluble antigens in dendritic cells. J Exp Med. 2007;204:2889-97 pubmed
- Aoki K, Nakamura T, Fujikawa K, Matsuda M. Local phosphatidylinositol 3,4,5-trisphosphate accumulation recruits Vav2 and Vav3 to activate Rac1/Cdc42 and initiate neurite outgrowth in nerve growth factor-stimulated PC12 cells. Mol Biol Cell. 2005;16:2207-17 pubmed..Depletion of Vav2 and Vav3 by RNA interference significantly inhibited both Rac1/Cdc42 activation and the formation of short ..
- Dong Z, Davidson D, Pérez Quintero L, Kurosaki T, Swat W, Veillette A. The adaptor SAP controls NK cell activation by regulating the enzymes Vav-1 and SHIP-1 and by enhancing conjugates with target cells. Immunity. 2012;36:974-85 pubmed publisher..These data showed that SAP secures NK cell activation by a dichotomous molecular mechanism, which is required for conjugate formation. These findings may have implications for the role of SAP in other immune cell types. ..
- 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. ..
- 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..Although Vav1 expression is restricted to the immune system, Vav2 and Vav3 are expressed in several tissues, including highly vascularized organs...
- Hebeis B, Vigorito E, Kovesdi D, Turner M. Vav proteins are required for B-lymphocyte responses to LPS. Blood. 2005;106:635-40 pubmed..following administration of low doses of LPS but respond normally to higher doses, while mice lacking both Vav1 and Vav2 manifest defective responses even after a high dose of LPS...
- Janas M, Turner M. Interaction of Ras with p110? is required for thymic ?-selection in the mouse. J Immunol. 2011;187:4667-75 pubmed publisher..Uncoupling Ras from p110? provides unambiguous identification of a Ras interaction required for thymic ?-selection. ..
- Yamauchi J, Chan J, Shooter E. Neurotrophins regulate Schwann cell migration by activating divergent signaling pathways dependent on Rho GTPases. Proc Natl Acad Sci U S A. 2004;101:8774-9 pubmed..Schwann cell migration dramatically by Src kinase-dependent activation of the guanine-nucleotide exchange factor Vav2 and RhoA...
- Menacho Márquez M, Nogueiras R, Fabbiano S, Sauzeau V, Al Massadi O, Dieguez C, et al. Chronic sympathoexcitation through loss of Vav3, a Rac1 activator, results in divergent effects on metabolic syndrome and obesity depending on diet. Cell Metab. 2013;18:199-211 pubmed publisher..These results indicate that the sympathetic system plays divergent roles in the etiology of metabolic diseases depending on food regimen, sympathoexcitation source, and disease stage. ..
- Weckbecker G, Bruns C, Fischer K, Heusser C, Li J, Metzler B, et al. Strongly reduced alloreactivity and long-term survival times of cardiac allografts in Vav1- and Vav1/Vav2-knockout mice. Transpl Int. 2007;20:353-64 pubmed..We have studied the role of Vav1 and Vav2 in allogeneic T-cell activation, antibody responses and allograft rejection...
- Tartare Deckert S, Monthouel M, Charvet C, Foucault I, Van Obberghen E, Bernard A, et al. Vav2 activates c-fos serum response element and CD69 expression but negatively regulates nuclear factor of activated T cells and interleukin-2 gene activation in T lymphocyte. J Biol Chem. 2001;276:20849-57 pubmedVav1 and Vav2 are members of the Dbl family of guanine nucleotide exchange factors for the Rho family of small GTPases...
- 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..Here we demonstrate that deficiency of Vav2 and Vav3, guanine nucleotides exchange factors for Rho guanosine triphosphatases, leads to an ocular phenotype ..
- Acton S, Astarita J, Malhotra D, Lukacs Kornek V, Franz B, Hess P, et al. Podoplanin-rich stromal networks induce dendritic cell motility via activation of the C-type lectin receptor CLEC-2. Immunity. 2012;37:276-89 pubmed publisher..Thus, activation of CLEC-2 by PDPN rearranges the actin cytoskeleton in DCs to promote efficient motility along stromal surfaces. ..
- Servitja J, Marinissen M, Sodhi A, Bustelo X, Gutkind J. Rac1 function is required for Src-induced transformation. Evidence of a role for Tiam1 and Vav2 in Rac activation by Src. J Biol Chem. 2003;278:34339-46 pubmed..We further show that Vav2 and the ubiquitously expressed Rac1 guanine nucleotide exchange factor Tiam1 are phosphorylated in tyrosine ..
- Fukumoto Y, Kurita S, Takai Y, Ogita H. Role of scaffold protein afadin dilute domain-interacting protein (ADIP) in platelet-derived growth factor-induced cell movement by activating Rac protein through Vav2 protein. J Biol Chem. 2011;286:43537-48 pubmed publisher..Furthermore, ADIP interacted with Vav2, a GDP/GTP exchange factor for Rac, in a Src phosphorylation-dependent manner, suggesting that ADIP mediates the ..
- Menacho Márquez M, García Escudero R, Ojeda V, Abad A, Delgado P, Costa C, et al. The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops. PLoS Biol. 2013;11:e1001615 pubmed publisher..Using genetically engineered mice, we show here that Vav2 and Vav3 favor cooperatively the initiation and promotion phases of skin tumors...
- Spies T, DeMars R. Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporter. Nature. 1991;351:323-4 pubmed..No similar effect was observed in 721.174 mutant cells, in which a homozygous deletion includes PSF among several other closely linked genes. At least one of these genes may therefore also be required for PSF function. ..
- Damoulakis G, Gambardella L, Rossman K, Lawson C, Anderson K, Fukui Y, et al. P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils. J Cell Sci. 2014;127:2589-600 pubmed publisher..These findings thus have broad implications for our understanding of GPCR signalling to Rho GTPases and the actin cytoskeleton. ..
- Dumont C, Corsoni Tadrzak A, Ruf S, de Boer J, Williams A, Turner M, et al. Rac GTPases play critical roles in early T-cell development. Blood. 2009;113:3990-8 pubmed publisher..Furthermore, we found a similar novel phenotype in the absence of Vav1, Vav2, and Vav3, which function as guanine nucleotide exchange factors for Rac1 and Rac2...
- Arora P, Marignani P, McCulloch C. Collagen phagocytosis is regulated by the guanine nucleotide exchange factor Vav2. Am J Physiol Cell Physiol. 2008;295:C130-7 pubmed publisher..Analysis of collagen bead-associated proteins showed enrichment with Vav2, which correlated temporally with increased Rac1 activity...
- Roth S, Bergmann H, Jaeger M, Yeroslaviz A, Neumann K, Koenig P, et al. Vav Proteins Are Key Regulators of Card9 Signaling for Innate Antifungal Immunity. Cell Rep. 2016;17:2572-2583 pubmed publisher..Here, we identify Vav proteins as key activators of the Card9 pathway. Vav1, Vav2, and Vav3 cooperate downstream of Dectin-1, Dectin-2, and Mincle to engage Card9 for NF-?B control and ..
- Robles Valero J, Lorenzo Martín L, Menacho Márquez M, Fernández Pisonero I, Abad A, Camos M, et al. A Paradoxical Tumor-Suppressor Role for the Rac1 Exchange Factor Vav1 in T Cell Acute Lymphoblastic Leukemia. Cancer Cell. 2017;32:608-623.e9 pubmed publisher..The downregulation of Vav1 is essential for the pathogenesis of human T-ALL of the TLX+ clinical subtype, further underscoring the suppressor role of this pathway. ..
- Boyle K, Gyori D, Sindrilaru A, Scharffetter Kochanek K, Taylor P, MÃ³csai A, et al. Class IA phosphoinositide 3-kinase Î² and Î´ regulate neutrophil oxidase activation in response to Aspergillus fumigatus hyphae. J Immunol. 2011;186:2978-89 pubmed publisher..These results start to define the signaling network controlling neutrophil ROS responses to A. fumigatus hyphae. ..
- Kant S, Swat W, Zhang S, Zhang Z, Neel B, Flavell R, et al. TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway. Genes Dev. 2011;25:2069-78 pubmed publisher..We show that this pathway is essential for full MAP kinase activation during the response to TNF. Moreover, this MLK pathway contributes to inflammation in vivo. ..
- Zhu S, Zhao C, Wu Y, Yang Q, Shao A, Wang T, et al. Identification of a Vav2-dependent mechanism for GDNF/Ret control of mesolimbic DAT trafficking. Nat Neurosci. 2015;18:1084-93 pubmed publisher..Here we show that the Rho-family guanine nucleotide exchange factor protein Vav2 is required for DAT cell surface expression and transporter activity modulated by glial cell line-derived ..
- Stephenson L, Miletic A, Kloeppel T, Kusin S, Swat W. Vav proteins regulate the plasma cell program and secretory Ig production. J Immunol. 2006;177:8620-5 pubmed..These data indicate a previously unknown role for Vav as an upstream regulator of Blimp-1. ..
- Duan L, Raja S, Chen G, Virmani S, Williams S, Clubb R, et al. Negative regulation of EGFR-Vav2 signaling axis by Cbl ubiquitin ligase controls EGF receptor-mediated epithelial cell adherens junction dynamics and cell migration. J Biol Chem. 2011;286:620-33 pubmed publisher..we demonstrate that stimulation of EGFR on human mammary epithelial cells disrupts adherens junctions (AJs) through Vav2 and Rac1/Cdc42 activation...
- 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. ..
- Madureira P, Matos P, Soeiro I, Dixon L, Simas J, Lam E. Murine gamma-herpesvirus 68 latency protein M2 binds to Vav signaling proteins and inhibits B-cell receptor-induced cell cycle arrest and apoptosis in WEHI-231 B cells. J Biol Chem. 2005;280:37310-8 pubmed..Subsequent yeast two-hybrid interaction studies showed that M2 also binds to Vav2, but not Vav3, and that three "PXXP" motifs located at the C terminus of M2 are important for this ..
- Liu J, Seno H, Miletic A, Mills J, Swat W, Stappenbeck T. Vav proteins are necessary for correct differentiation of mouse cecal and colonic enterocytes. J Cell Sci. 2009;122:324-34 pubmed publisher..Loss of Vav protein expression in triple-knockout mice (Vav1(-/-);Vav2(-/-);Vav3(-/-)) resulted in defective expansion of microtubule cytoskeletons, a significant decrease in cell height ..
- Gavard J, Gutkind J. VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin. Nat Cell Biol. 2006;8:1223-34 pubmed publisher..is initiated by the activation of the small GTPase Rac by VEGFR-2 through the Src-dependent phosphorylation of Vav2, a guanine nucleotide-exchange factor...
- Glassmann A, Topka S, Wang Eckardt L, Anders S, Weisheit G, Endl E, et al. Basic molecular fingerprinting of immature cerebellar cortical inhibitory interneurons and their precursors. Neuroscience. 2009;159:69-82 pubmed publisher..Together, these data support the notion that diversification of cerebellar inhibitory interneurons is highly regulative and subject to local signaling to postmigratory precursors. ..
- Nordstrand L, Svärd J, Larsen E, Nilsen A, Ougland R, Furu K, et al. Mice lacking Alkbh1 display sex-ratio distortion and unilateral eye defects. PLoS ONE. 2010;5:e13827 pubmed publisher..Genetic and phenotypic assessment suggests that Alkbh1 mediates gene regulation in spermatogenesis, and that Alkbh1 is essential for normal sex-ratio distribution and embryonic development in mice. ..
- Conley S, Abais Battad J, Yuan X, Zhang Q, Boini K, Li P. Contribution of guanine nucleotide exchange factor Vav2 to NLRP3 inflammasome activation in mouse podocytes during hyperhomocysteinemia. Free Radic Biol Med. 2017;106:236-244 pubmed publisher..The present study tested whether the guanine nucleotide exchange factor Vav2 mediates Rac1-mediated NOX activation in response to elevated Hcys leading to NLRP3 inflammasome ..
- Quesnel Vallieres M, Dargaei Z, Irimia M, Gonatopoulos Pournatzis T, Ip J, Wu M, et al. Misregulation of an Activity-Dependent Splicing Network as a Common Mechanism Underlying Autism Spectrum Disorders. Mol Cell. 2016;64:1023-1034 pubmed publisher..Collectively, our results provide evidence that misregulation of an nSR100-dependent splicing network controlled by changes in neuronal activity is causally linked to a substantial fraction of autism cases. ..
- Johansson M, Taylor M, Jagodic M, Tus K, Schatzle J, Wakeland E, et al. Mapping of quantitative trait loci determining NK cell-mediated resistance to MHC class I-deficient bone marrow grafts in perforin-deficient mice. J Immunol. 2006;177:7923-9 pubmed..This study describes the first important step toward identifying BM graft resistance gene(s). ..
- Pan D, Amison R, Riffo Vasquez Y, Spina D, Cleary S, Wakelam M, et al. P-Rex and Vav Rac-GEFs in platelets control leukocyte recruitment to sites of inflammation. Blood. 2015;125:1146-58 pubmed publisher..Therefore, platelet P-Rex and Vav family Rac-GEFs play important proinflammatory roles in leukocyte recruitment. ..
- Fabbiano S, Menacho MÃ¡rquez M, Sevilla M, AlbarrÃ¡n JuÃ¡rez J, Zheng Y, Offermanns S, et al. Genetic dissection of the vav2-rac1 signaling axis in vascular smooth muscle cells. Mol Cell Biol. 2014;34:4404-19 pubmed publisher..Here, we show that the expression of an active version of the Rac1 activator Vav2 exclusively in vSMCs leads to hypotension as well as the elimination of the hypertension induced by the systemic ..
- Johannes F, Blizard D, Lionikas A, Lang D, Vandenbergh D, Stout J, et al. QTL influencing baseline hematocrit in the C57BL/6J and DBA/2J lineage: age-related effects. Mamm Genome. 2006;17:689-99 pubmed..Baseline serum hematocrit is influenced by several QTL that appear to vary with the age and sex of the animal. These QTL primarily overlap with QTL that have been shown to regulate hematopoietic stem cell phenotypes. ..
- Pearce A, Wilde J, Doody G, Best D, Inoue O, Vigorito E, et al. Vav1, but not Vav2, contributes to platelet aggregation by CRP and thrombin, but neither is required for regulation of phospholipase C. Blood. 2002;100:3561-9 pubmed..the role of the Rho and Rac family small guanine triphosphate (GTP) exchange factors (RhoGEFs), Vav1 and Vav2, in the activation of platelets by the immunoreceptor tyrosine-based activation motif (ITAM)-coupled collagen ..
- Wells C, Bhavsar P, Evans I, Vigorito E, Turner M, Tybulewicz V, et al. Vav1 and Vav2 play different roles in macrophage migration and cytoskeletal organization. Exp Cell Res. 2005;310:303-10 pubmed..Using mice deficient for Vav1, Vav2 and/or Vav3, overlapping and isoform-specific functions of the three Vav proteins have been described in various ..
- Rahaman S, Swat W, Febbraio M, Silverstein R. Vav family Rho guanine nucleotide exchange factors regulate CD36-mediated macrophage foam cell formation. J Biol Chem. 2011;286:7010-7 pubmed publisher..These studies for the first time link CD36 and Vavs in a signaling pathway required for macrophage foam cell formation. ..
- Gmyrek G, Akilesh H, Graham D, Fuchs A, Yang L, Miller M, et al. Loss of DAP12 and FcR? drives exaggerated IL-12 production and CD8(+) T cell response by CCR2(+) Mo-DCs. PLoS ONE. 2013;8:e76145 pubmed publisher..Our data suggest a novel cross-talk between DC-ITAM and GM-CSF signaling pathways, which controls Mo-DC differentiation, IL-12 production, and CD8(+) T cell responses. ..
- Martin H, Mali R, Ma P, Chatterjee A, Ramdas B, Sims E, et al. Pak and Rac GTPases promote oncogenic KIT-induced neoplasms. J Clin Invest. 2013;123:4449-63 pubmed publisher..These studies identify Pak and Rac GTPases, including Vav1, as potential therapeutic targets in MPN and AML involving an oncogenic form of KIT. ..
- Fabbiano S, Menacho MÃ¡rquez M, Robles Valero J, Pericacho M, Matesanz MarÃn A, GarcÃa MacÃas C, et al. Immunosuppression-Independent Role of Regulatory T Cells against Hypertension-Driven Renal Dysfunctions. Mol Cell Biol. 2015;35:3528-46 pubmed publisher..These results indicate that TREG cells constitute a first protective barrier against hypertension-driven tissue fibrosis and, in addition, suggest new therapeutic avenues to prevent hypertension-linked cardiorenal diseases. ..
- Latreille R, Servant R, Darsigny M, Marcoux S, Jones C, Perreault N, et al. Transcription factor CUX1 is required for intestinal epithelial wound healing and targets the VAV2-RAC1 Signalling complex. Biochim Biophys Acta Mol Cell Res. 2017;1864:2347-2355 pubmed publisher..Chromatin immunoprecipitation assays identified the guanine nucleotide exchange factor Vav2 gene as a direct target for CUX1...