Affinage

VAV2

Guanine nucleotide exchange factor VAV2 · UniProt P52735

Length
878 aa
Mass
101.3 kDa
Annotated
2026-06-11
100 papers in source corpus 59 papers cited in narrative 59 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VAV2 is a ubiquitously functioning RHO-family guanine nucleotide exchange factor that converts tyrosine-kinase signaling into actin cytoskeletal remodeling by catalyzing GDP→GTP exchange on Rac1, Cdc42, and RhoA, with an in vitro preference of Rac1 > Cdc42 > RhoA (PMID:9822605, PMID:10744696, PMID:15850391). Its activity is switched on by tyrosine phosphorylation on N-terminal residues Tyr-142/159/172 imposed by receptor tyrosine kinases (EGFR, PDGFR, VEGFR2) and the non-receptor kinase Src downstream of diverse adhesion and growth-factor cues (PMID:10618391, PMID:12454019, PMID:17686471, PMID:19755152), while its catalytic output is further gated by PI3-kinase: the PH domain and the cysteine-rich domain act as positive modulators of exchange activity, the CRD contacting Rac1 directly to influence catalysis (PMID:12454019, PMID:11909943, PMID:15850391). The SH2 domain provides the recruitment logic of the protein, binding phosphotyrosine motifs in activated receptors and scaffolds—including Arap3, TXNIP, EphA2, cortactin, and APP—and additionally engaging the membrane lipids PIP2 and PIP3, thereby directing VAV2 to sites of signaling such as invadopodia where it drives Rac3-dependent matrix degradation (PMID:22750419, PMID:26919541, PMID:28356423, PMID:32897354, PMID:35882892). Through these GTPase outputs VAV2 controls cell spreading, migration, invasion, and neurite outgrowth in contexts ranging from integrin- and cadherin-based adhesion to growth-factor-driven motility, and EGFR–VAV2–Rac1 signaling is sustained on endosomes to support chemotaxis (PMID:11448999, PMID:15728722, PMID:28356423, PMID:39744818). In vivo, VAV2 is required for B-cell maturation and humoral immunity (PMID:11376342, PMID:11376343), for nitric-oxide-triggered vascular smooth-muscle relaxation and blood-pressure control via a Rac1–Pak1–PDE5 axis (PMID:20038798, PMID:25288640), for GDNF/Ret-dependent dopamine transporter trafficking (PMID:26147533), and for insulin/IGF1 responsiveness and muscle mass through catalysis-dependent modulation of PI3K signaling (PMID:33199701); in epithelial and cancer cells its catalytic activity drives proliferative and pro-rRNA transcriptional programs through c-Myc and YAP/TAZ (PMID:32963234, PMID:38374399). VAV2 is negatively regulated by PTP-PEST dephosphorylation and Cbl-mediated ubiquitination of the phosphorylated protein (PMID:16513648, PMID:20940296), and beyond its GEF role it forms a Ku70/Ku80 complex contributing to non-homologous end joining repair (PMID:34462423).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1998 High

    Established VAV2 as a phosphotyrosine-regulated exchange factor for Rho-family GTPases, defining the core enzymatic identity of the protein and linking its catalytic output to oncogenic transformation.

    Evidence In vitro GEF assays and NIH-3T3 transformation with cytoskeletal readouts

    PMID:9822605

    Open questions at the time
    • Did not resolve full substrate spectrum or the structural basis of phosphorylation-dependent activation
  2. 2000 High

    Defined the substrate range (Cdc42, Rac1, RhoA) and showed that VAV2 is a direct substrate of and binds activated EGFR/PDGFR, connecting receptor tyrosine kinases to GTPase activation and migration.

    Evidence In vitro GEF assays with dominant-negative GTPase epistasis, MS phosphoproteomics, reciprocal co-IP, GTPase pull-downs and migration assays

    PMID:10618391 PMID:10744696 PMID:10982832

    Open questions at the time
    • Phosphosites and the relative contributions of phosphorylation versus PI3K to activation were not yet defined
    • Did not distinguish receptor- from integrin-driven inputs
  3. 2002 High

    Mapped EGFR phosphorylation to N-terminal Tyr-142/159/172 and the SH2-bound receptor sites, and revealed that exchange activity is gated primarily by PI3K through the PH domain rather than by phosphotyrosine level alone.

    Evidence In vitro kinase assay with purified EGFR/VAV2, site-directed mutagenesis, PI3K inhibition and Rac exchange assays

    PMID:12454019

    Open questions at the time
    • Did not establish how PH/lipid engagement is coupled to catalysis at atomic resolution
  4. 2002 High

    Dissected the autoinhibition/activation logic by showing the PH domain controls signaling, membrane association and transformation while the CRD is essential for catalysis, with PI3K synergizing with transforming activity.

    Evidence PH and CRD mutagenesis with in vitro GEF assays, transformation, membrane fractionation and PI3K modulation

    PMID:11909943

    Open questions at the time
    • Mechanistic coupling between CRD-GTPase contact and exchange kinetics not yet quantified
  5. 2005 High

    Provided the kinetic and structural mechanism of catalysis, showing a Theorell-Chance exchange with Rac1>Cdc42>RhoA preference and direct CRD-Rac1 contact governing kon and kcat.

    Evidence In vitro GEF kinetics, fluorescence anisotropy, NMR chemical-shift mapping and Rac1/CRD mutagenesis

    PMID:15850391

    Open questions at the time
    • Did not address how phosphorylation relieves autoinhibition in the full-length protein
  6. 2001 High

    Resolved how VAV2 is positioned for activation, demonstrating SH2-mediated membrane targeting is required for in-cell phosphorylation and that Src and integrin engagement drive Rac activation during spreading.

    Evidence SH2 and DH mutants, in vitro/in vivo phosphorylation assays, Src inhibition and fibronectin spreading assays

    PMID:11448999 PMID:11516622

    Open questions at the time
    • Integrin-to-VAV2 signaling intermediates were not fully ordered
  7. 2001 High

    Established the physiological requirement for VAV2 in B-cell biology, showing it relays BCR/CD19 signaling to calcium flux and NFAT and is required for humoral immunity and B-cell maturation.

    Evidence Vav2 and Vav1/Vav2 knockout mice, co-IP with CD19, NFAT reporter, calcium flux and B-cell developmental analysis

    PMID:11080163 PMID:11376342 PMID:11376343

    Open questions at the time
    • Functional redundancy with Vav1/Vav3 complicates assignment of VAV2-specific contributions
  8. 2004 Medium

    Extended the upstream input map by identifying Nek3 and nectin/c-Src as activators, and showed c-Src-phosphorylated Cdc42 can boost VAV2 GEF activity toward Rac1, indicating layered co-activation.

    Evidence Yeast two-hybrid, co-IP, kinase assays, dominant-negative VAV2 and Rac activation assays

    PMID:15485841 PMID:15618286

    Open questions at the time
    • Single-lab epistasis without structural validation of the proposed co-activation
    • Tyr versus Ser phosphorylation contributions to activation not separated
  9. 2007 High

    Embedded VAV2 in receptor- and adhesion-driven motility programs, identifying it as the Rac-GEF for VEGFR2/Src signaling in endothelial migration and for EGFR autocrine-driven invasion in carcinoma.

    Evidence GEF-trapping with nucleotide-free Rac1, siRNA, VEGFR2/Src/EGFR inhibition and migration/invasion assays

    PMID:17234718 PMID:17686471

    Open questions at the time
    • Did not define how sustained versus transient Rac1 activation is achieved
    • Substrate selection (Rac1 vs RhoA) in different receptor contexts unresolved
  10. 2009 High

    Defined the in vivo vascular function of VAV2, placing it in a Rac1-Pak1-PDE5 axis that drives nitric-oxide-dependent smooth-muscle relaxation and controls blood pressure, with pharmacological rescue.

    Evidence Vav2 knockout mice, Pak1-PDE5 co-IP, autophosphorylation assays, PDE5 inhibition and blood-pressure measurement

    PMID:17202406 PMID:20038798

    Open questions at the time
    • How VAV2 is activated in resting/contracting smooth muscle in vivo not fully defined
  11. 2010 Medium

    Identified the negative regulatory arm of the pathway, showing PTP-PEST dephosphorylates VAV2 and Cbl ubiquitinates phospho-VAV2 to terminate Rac1/Cdc42 signaling, and revealed a VAV2 role in EGFR trafficking.

    Evidence PTP-PEST knockout cells, Cbl mutants and ubiquitination assays, GEF-deficient VAV2, co-localization with Rab5/EGFR

    PMID:16513648 PMID:20140013 PMID:20940296

    Open questions at the time
    • Single-lab studies for each regulator without cross-validation
    • Stoichiometry and timing of dephosphorylation vs ubiquitination not resolved
  12. 2014 Medium

    Linked VAV2 to focal-adhesion and scaffold machinery (vimentin, PKL/GIT2, FLNB, ADIP) that organize its activation and direct persistent, polarized migration and angiogenesis.

    Evidence Phosphoproteomics, co-IP, siRNA knockdown, constitutively active Rac1 rescue and directional migration assays

    PMID:20110358 PMID:22027834 PMID:23615439 PMID:24858039

    Open questions at the time
    • Most interactions rest on single-lab co-IP without reciprocal structural validation
    • Hierarchy among scaffolds at a single adhesion site not defined
  13. 2014 High

    Genetically separated VAV2 from its effector by showing Rac1-specific deletion in smooth muscle reproduces Vav2-KO hypertension, while Rac1 (not VAV2) is additionally needed for neointima formation.

    Evidence Cell-type-specific inducible Cre-loxP mouse models with blood-pressure and vascular readouts

    PMID:25288640

    Open questions at the time
    • Did not address VAV2-independent Rac1 activation sources in vSMCs
  14. 2016 High

    Defined high-resolution recognition rules for the VAV2 SH2 domain, solving structures with Arap3, TXNIP and APP phosphopeptides and showing it also binds PIP2/PIP3 and EphA2 phospho-juxtamembrane region on membranes.

    Evidence NMR and crystal structures, ITC, lipid nanodisc binding and cellular co-IP

    PMID:22750419 PMID:26919541 PMID:32897354 PMID:35882892

    Open questions at the time
    • Functional consequence of each SH2 partner interaction beyond binding largely uncharacterized
    • How lipid versus phosphopeptide binding compete in vivo unresolved
  15. 2017 High

    Defined how SH2-mediated recruitment to phospho-cortactin localizes VAV2 to invadopodia where it activates Rac3 to drive matrix degradation, connecting recruitment specificity to invasive function.

    Evidence SH2 binding screen, phosphopeptide assays, SH2 mutants, siRNA/rescue and Rac3 FRET biosensor

    PMID:28356423

    Open questions at the time
    • Why Rac3 rather than Rac1 is the invadopodial substrate not mechanistically explained
  16. 2020 High

    Demonstrated catalysis-dependent physiological roles in vivo using activity-tuned knock-in mice, showing VAV2 catalysis sets skeletal-muscle insulin/IGF1 responsiveness and muscle mass, and revealed Cdc42-selective signaling distinguishing VAV2 from VAV1.

    Evidence Hypo-/hyperactive Vav2 knock-in mice with metabolic readouts; in vivo GEF-trapping and Vav1 F56W mutagenesis with Ca2+ entry assays

    PMID:31974114 PMID:33199701

    Open questions at the time
    • Tissue-specific substrate choice between Rac1 and Cdc42 in vivo not fully mapped
  17. 2024 Medium

    Connected VAV2 catalytic output to transcriptional and biosynthetic reprogramming in epithelial/cancer cells via RHO GTPases→PAK/ROCK→c-Myc/YAP-TAZ driving proliferation, poor differentiation and RNA Pol I-dependent ribosome biogenesis.

    Evidence Catalysis-dead mutants, transcriptomics, pre-rRNA/RNA Pol I assays in keratinocytes and patient-derived hnSCC/OSCC cells

    PMID:32963234 PMID:38374399

    Open questions at the time
    • Single-lab pathway placement; direct GTPase-to-transcription-factor links not biochemically reconstituted
  18. 2021 Medium

    Uncovered a non-canonical GEF-independent function of VAV2 in DNA repair, showing it is required for Ku70/Ku80 complex formation and NHEJ and confers radioresistance through STAT1.

    Evidence Knockdown/overexpression, Ku70/Ku80 co-IP, DNA repair assays and in vivo xenograft radiotherapy

    PMID:34462423

    Open questions at the time
    • Single-lab finding; how a cytoplasmic GEF accesses nuclear NHEJ machinery is unexplained
    • Whether catalytic activity is dispensable for this role not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the SH2 recruitment repertoire, lipid binding, PI3K gating and phosphorylation jointly select among Rac1/Rac3/Cdc42/RhoA substrates in each physiological context, and whether the non-canonical NHEJ role is mechanistically separable from GEF activity.
  • No unified structural model of full-length VAV2 activation in a membrane context
  • Substrate-selection determinants across tissues not defined
  • Mechanism connecting cytoplasmic VAV2 to nuclear Ku70/Ku80 unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0008092 cytoskeletal protein binding 3 GO:0060089 molecular transducer activity 3 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 2 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 1
Partners
APPCBLCDC42CORTACTINEGFRRAC1RHOASRC
Complex memberships
Ku70/Ku80 complex

Evidence

Reading pass · 59 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 VAV2 acts as a guanine nucleotide exchange factor (GEF) for RhoG and RhoA-like GTPases in a phosphotyrosine-dependent manner; oncogenic activation of VAV2 correlates with acquisition of phosphorylation-independent exchange activity; co-expression of RhoA enhances VAV2 oncogenic activation by tyrosine kinases. In vitro GEF assays, NIH-3T3 transformation assays, transient transfection with cytoskeletal readouts The EMBO journal High 9822605
2000 VAV2 functions as a potent GEF for Cdc42, Rac1, and RhoA in vitro; constitutively active VAV2 activates JNK and induces lamellipodia/membrane ruffles; VAV2-transformed NIH 3T3 cells show elevated Rac-GTP levels; transforming activity requires Cdc42, Rac1, and RhoA function. In vitro GEF assays, NIH 3T3 transformation with dominant-negative GTPases, JNK activation assay, GTP-loading measurement The Journal of biological chemistry High 10744696
2000 VAV2 is tyrosine phosphorylated in response to EGF and PDGF and associates with EGFR and PDGFR in vivo; the SH2 domain of VAV2 mediates binding to the activated EGFR; VAV2 is identified as a substrate of both EGFR and PDGFR. Mass spectrometry of EGF-induced phosphoproteins, co-immunoprecipitation, in vivo phosphorylation assays Proceedings of the National Academy of Sciences of the United States of America High 10618391
2000 VAV2 activates Rac1, Cdc42, and RhoA downstream of EGF and PDGF growth factor receptors but not downstream of beta1 integrins in fibroblasts; constitutively active VAV2 induces membrane ruffles and elevated cell migration; elevated migration is blocked by dominant-negative Rac1 and Cdc42; a C-terminal VAV2 fragment acts as dominant-negative to decrease EGF-induced Rac1 activity. GFP-fusion overexpression, GTPase pull-down activity assays, dominant-negative co-expression, cell migration assays, tyrosine phosphorylation analysis Molecular and cellular biology High 10982832
2002 EGFR phosphorylates VAV2 exclusively on its N-terminal domain at Tyr-142, Tyr-159, and Tyr-172 in vitro; VAV2 SH2 domain binds preferentially to EGFR autophosphorylation sites Tyr-992 and Tyr-1148; VAV2 exchange activity on Rac is stimulated by EGF but regulated primarily through PI3-kinase activation (PH domain dependency), not by tyrosine phosphorylation level; a point mutation in the PH domain or PI3K inhibition blocks VAV2 exchange activity and membrane ruffling. In vitro protein kinase assay with purified EGFR and VAV2, site-directed mutagenesis, PI3K inhibitor treatment, Rac exchange activity assay, co-immunoprecipitation The Journal of biological chemistry High 12454019
2001 VAV2 is required for cell spreading on fibronectin in NIH3T3 fibroblasts specifically by enabling lamellipodia formation; a DH-domain mutant of VAV2 acts as dominant-negative to block integrin-dependent (but not growth factor-dependent) Rac activation; VAV2-mediated Rac activation is Src-dependent in vivo; PH domain mutation eliminates exchange activity. Dominant-negative DH mutant expression, Rac-GTP measurement, Src inhibitor PP2 treatment, dominant-negative Src co-expression, fibronectin spreading assays The Journal of cell biology High 11448999
2001 VAV2 membrane-targeting via its SH2 domain is required for tyrosine phosphorylation by activated EGFR in intact cells; the N-terminal domain alone is phosphorylated by EGFR in vitro but not in vivo unless linked to the SH2 domain. GFP-fusion constructs, SH2 domain point mutations, in vitro kinase assay, EGF-stimulation phosphorylation assays in COS7 cells Cellular signalling Medium 11516622
2001 VAV2 is tyrosine phosphorylated after BCR engagement; it physically interacts with CD19 co-receptor and synergistically enhances VAV2 phosphorylation upon BCR stimulation; VAV2 potentiates NFAT-dependent transcription and sustained calcium flux in B cells (but not T cells); this requires functional DH and SH2 domains and the N-terminus. Co-immunoprecipitation, NFAT reporter assay, calcium flux measurement, domain deletion/mutation analysis, Jurkat and B cell transfection The EMBO journal Medium 11080163
2001 CD44v3 and VAV2 form a physical complex in ovarian tumor cells; the SH3-SH2-SH3 domain of VAV2 binds the cytoplasmic domain of CD44; HA binding to CD44v3 activates VAV2-mediated Rac1 signaling; Grb2 (bound to p185HER2) associates with the CD44v3-VAV2 complex upon HA stimulation, leading to Ras activation and tumor cell growth. Co-immunoprecipitation, in vitro binding assays with recombinant VAV2 fragments, Rac1 activation assays, Ras activation assays, dominant-negative Grb2 mutant expression The Journal of biological chemistry Medium 11606575
2001 VAV2 is required for humoral immune responses; Vav2-deficient mice are defective in TD and TI-II antigen responses, Ig class-switching, germinal center formation, and secondary responses; combined Vav1/Vav2 deficiency causes reduced B cell numbers and a maturational block, with poor BCR-driven proliferation and calcium release. Vav2 knockout mice, immunization assays, B cell developmental analysis, proliferation and calcium flux assays Nature immunology High 11376342
2001 Combined deletion of Vav1 and Vav2 causes marked reduction in mature B lymphocytes and abolishes BCR-driven proliferation and thymus-independent antigen responses; Vav1/Vav2 double-KO B cells show greatly impaired BCR-stimulated intracellular calcium mobilization. Double-knockout mice (Vav1-/-Vav2-/-), flow cytometry, proliferation assays, calcium flux measurement Nature immunology High 11376343
2002 PH domain mutations impair VAV2 signaling, transforming activity, and membrane association but do not affect exchange activity on Rac in vitro (slight effect on RhoA/Cdc42); the cysteine-rich domain (CRD) is critical for exchange activity in vitro and contributes to VAV2 membrane localization; PI3K activation synergistically enhances VAV2 transforming activity by stimulating exchange activity. Site-directed mutagenesis of PH domain and CRD, in vitro GEF assays, NIH 3T3 transformation, membrane fractionation, PI3K inhibitor/activator treatments Molecular and cellular biology High 11909943
2003 VAV2 is tyrosine phosphorylated in cells expressing active/oncogenic Src; VAV2 acts as a downstream effector of Src to regulate Rac1-dependent pathways contributing to cell transformation. Immunoprecipitation/phosphotyrosine blotting, Src inhibitor SU6656, activated Rac1 measurement in Src-transformed cells The Journal of biological chemistry Medium 12810717
2003 EGFR activation by integrin-mediated adhesion (in the absence of EGF) activates Rac via VAV2 and PI3-kinase; inhibition of EGFR activity prevents adhesion-induced Rac-GTP loading, cell spreading and lamellipodia; dominant-active PI3K restores Rac loading under EGFR inhibition; VAV2 is identified as a crucial downstream component of the EGFR-PI3K-Rac pathway during integrin-mediated adhesion. EGFR kinase inhibitors, dominant-active/negative PI3K constructs, Rac-GTP pull-down assay, cell spreading/lamellipodia assays, VAV2 functional studies Oncogene Medium 12955089
2004 VAV2 is the Rac-GEF responsible for nectin-induced Rac activation; nectins recruit and tyrosine-phosphorylate VAV2 through c-Src at nectin-based cell-cell contact sites; c-Src-phosphorylated Cdc42 enhances the GEF activity of tyrosine-phosphorylated VAV2 on Rac1; Cdc42 is not required for VAV2 recruitment or c-Src-mediated VAV2 phosphorylation. Dominant-negative VAV2 expression, co-immunoprecipitation, tyrosine phosphorylation assays, Rac activation assays, cell-cell adhesion assays The Journal of biological chemistry Medium 15485841
2005 VAV2-mediated nucleotide exchange on Rho GTPases follows the Theorell-Chance mechanism; GTPase specificity order in vitro is Rac1 > Cdc42 > RhoA; the CRD domain directly associates with Rac1 (NMR chemical shift mapping) and affects both k_on and k_cat for VAV2-mediated nucleotide exchange; residues K116 and S83 of Rac1 at the P-loop and guanine base are part of the CRD binding interface. In vitro GEF kinetic assays, fluorescence anisotropy, NMR chemical shift mapping, site-directed mutagenesis of Rac1 and VAV2 CRD Biochemistry High 15850391
2005 Local accumulation of PIP3 recruits VAV2 and VAV3 to activate Rac1/Cdc42 at protruding sites during NGF-induced neurite outgrowth in PC12 cells; VAV2/VAV3 and PI3-kinase form a positive feedback loop; depletion of VAV2 and VAV3 by RNAi inhibits both Rac1/Cdc42 activation and short process formation leading to neurite outgrowth. FRET activity probes (live imaging), siRNA knockdown, PI3K inhibitor, subcellular localization imaging Molecular biology of the cell High 15728722
2006 Trans-interacting cadherin activates Rac through a c-Src → Vav2 + Rap1 (via C3G/Crk) → PI3K pathway; c-Src phosphorylates VAV2 but this alone is insufficient for VAV2 activation; Rap1 additionally activates PI3K, which is required for VAV2 activation; activated Rap1 alone cannot activate non-phosphorylated VAV2. Co-immunoprecipitation, dominant-negative constructs, Rac activation assay, cadherin-based adhesion assays in fibroblasts and epithelial cells Oncogene Medium 16170364
2006 CD47 promotes dendritic and axonal development in hippocampal neurons through Src-mediated activation of FRG (for Cdc42) and VAV2 (a GEF for Cdc42 and Rac); inhibition of VAV2 prevents CD47-promoted dendritic development; VAV2 acts downstream of Src in this pathway. VAV2 inhibitor expression, CD47 knockout neurons, overexpression assays, Src inhibitor treatment, dendritic morphology quantification The Journal of neuroscience Medium 17135401
2007 VAV2 mediates VEGF-induced Rac1 activation downstream of VEGFR-2 and Src kinase; VEGF treatment induces biphasic Rac1 activation; VAV2 associates with nucleotide-free Rac1 (G15ARac1) after VEGF stimulation; VAV2 is tyrosine phosphorylated by Src downstream of VEGFR-2; siRNA depletion of VAV2 prevents VEGF-induced Rac1 activation and impairs endothelial cell migration. Nucleotide-free Rac1 mutant binding assay, siRNA knockdown, VEGFR-2 and Src inhibitors, Rac1 activity assay, migration assay Experimental cell research High 17686471
2007 VAV2 is required for the EGFR autocrine loop-driven persistent Rac1 activation in head and neck squamous cell carcinoma cells; the EGFR/VAV2/Rac1 axis is crucial for acquisition of motile and invasive properties in most HNSCC cells. Rac1-GTP pull-down assay, siRNA knockdown of VAV2 and EGFR, cell invasion/migration assays, EGFR inhibition Carcinogenesis Medium 17234718
2006 VAV2 is required for neuronal migration stimulated by the adhesion molecule L1; L1 clustering activates VAV2 and downstream Pak1; Pak1 kinase activity contributes to L1-induced ERK activation and is necessary for L1-potentiated cell migration. VAV2 activation assay upon L1 clustering, Pak1 kinase assay, ERK activation measurement, migration assay Neuroreport Low 15597056
2007 VAV2 loss in mice causes tachycardia, hypertension, and cardiovascular/renal defects; the hypertensive phenotype arises from chronic stimulation of the renin/angiotensin II and sympathetic nervous systems. Vav2 knockout mouse, cardiovascular physiological measurements, pharmacological challenge Molecular biology of the cell Medium 17202406
2008 VAV2 collagen phagocytosis: VAV2 is enriched at collagen bead-binding sites; knockdown of VAV2 prevents collagen-induced Rac1 activation and collagen bead binding; VAV2 association with nucleotide-free Rac1 occurs after collagen binding; VAV2 phosphorylation during collagen binding requires Src kinase activity. siRNA knockdown, nucleotide-free Rac1 mutant pulldown, Rac1-GTP assay, Src inhibitor, collagen bead binding assay American journal of physiology. Cell physiology Medium 18434624
2008 In vascular smooth muscle cells, homocysteine activates VAV2 via ceramide-associated tyrosine phosphorylation, leading to Rac1 activation and consequent NADPH oxidase activation; VAV2 siRNA blocks Rac1 activity, NADPH oxidase-dependent superoxide production, and glomerulosclerosis during hyperhomocysteinemia in vivo. siRNA knockdown, Rac1 activity assay, superoxide production assay, dominant-active Vav2 (onco-Vav2) transfection, rat kidney in vivo model Hypertension Medium 19029489
2009 VAV2 is required for nitric oxide-triggered blood vessel relaxation and normal blood pressure in vascular smooth muscle cells; VAV2 activates Rac1, which activates Pak; autophosphorylated Pak1 physically interacts with and inhibits phosphodiesterase type 5 (without transphosphorylating it), promoting RhoA inactivation and F-actin depolymerization; pharmacological inhibition of PDE5 prevents hypertension in Vav2-knockout mice. Vav2 knockout mouse, Pak1/PDE5 co-immunoprecipitation, autophosphorylation assays, PDE5 inhibitor treatment, blood pressure measurement The Journal of clinical investigation High 20038798
2009 Mechanical stretch activates RhoA in mesangial cells via VAV2; stretch induces VAV2 tyrosine phosphorylation at Y172 (required for activation) through EGFR transactivation; Src and PI3K are required upstream of VAV2 and RhoA activation; EGFR and VAV2 physically associate after stretch in an EGFR activation-dependent manner. Dominant-negative VAV2 (Y172/159F), siRNA, EGFR inhibitor, Src and PI3K inhibitors, co-immunoprecipitation, RhoA activation assay Cellular signalling Medium 19755152
2010 PTP-PEST directly targets VAV2; PTP-PEST dephosphorylates and regulates VAV2 activity; in PTP-PEST null cells, VAV2 activity is enhanced, leading to increased Rac1 activity and exaggerated membrane protrusions; PTP-PEST couples protrusion and retraction by reciprocally modulating VAV2/Rac1 and p190RhoGAP/RhoA activities; VAV2 is regulated by integrin-mediated adhesion. PTP-PEST knockout fibroblasts, Rac1 and RhoA GTP-loading assays, VAV2 phosphorylation analysis, morphological analysis The Journal of biological chemistry Medium 16513648
2010 Cbl E3 ubiquitin ligase regulates phospho-VAV2 levels after EGFR stimulation; Cbl forms a complex with phospho-EGFR and phospho-VAV2 and facilitates phospho-VAV2 ubiquitinylation; Cbl interacts directly with VAV2 in a Cbl Tyr-700-dependent manner; Cbl-mediated ubiquitination attenuates VAV2-dependent Rac1/Cdc42 activation and adherens junction disruption. Co-immunoprecipitation, ubiquitinylation assay, Cbl point mutants, siRNA knockdown of Cbl, constitutively active VAV2 expression, Rac1/Cdc42 activity assays The Journal of biological chemistry Medium 20940296
2010 VAV2 expression delays EGFR internalization and degradation and enhances EGFR, ERK, and Akt phosphorylation; this effect depends on VAV2's GEF function; VAV2 co-localizes with EGFR and Rab5 in endosomes upon EGF stimulation; VAV2 interaction with endosome-associated proteins and RhoA function modulate its effect on EGFR stability. VAV2 overexpression/knockdown, EGFR degradation assay, confocal co-localization, GEF-deficient VAV2 mutant, phosphorylation analysis Oncogene Medium 20140013
2010 FLNB (filamin B) modulates Rac-1 localization and activity in endothelial cells; a signaling complex containing FLNB, Rac-1, and VAV2 exists under basal conditions and further interacts with VEGFR2 and integrin αvβ5 after VEGF stimulation; FLNB knockdown alters VAV2 activation and impairs VEGF-induced endothelial cell migration and angiogenesis. siRNA knockdown, co-immunoprecipitation, Rac-1 activity assay, in vitro angiogenesis/migration assay The Journal of biological chemistry Medium 20110358
2010 EphrinA5-mediated inhibition of Schwann cell migration is mediated via VAV2; ephrinA5 clustering increases VAV2 phosphorylation in Schwann cells; VAV2 knockdown abrogates ephrinA5-inhibitory effect on migration and improves Schwann-astrocyte intermingling; VAV2 mediates ephrinA5 inhibition of Schwann cell integrin signaling. siRNA knockdown of VAV2, VAV2 phosphorylation assay after ephrin clustering, migration assay on astrocyte monolayers The Journal of neuroscience Medium 20335460
2010 Balanced VAV2 GEF activity regulates neurite outgrowth and branching in Xenopus spinal neurons; VAV2 GEF activity activates Rac1 in spinal neurons; enhanced branching on L1 requires VAV2 GEF function; N-terminal tyrosine residues of VAV2 are required for LN-induced branching but not for protection from RhoA-mediated collapse. Gain- and loss-of-function VAV2 constructs in Xenopus spinal neurons (in vitro and in vivo), GEF-dead mutants, N-terminal tyrosine mutants, growth cone collapse assay Molecular and cellular neurosciences Medium 20298788
2004 Prolactin stimulates Nek3-VAV2 interaction with the prolactin receptor; Nek3 kinase activity increases VAV2 serine and tyrosine phosphorylation; both Nek3 and VAV2 are required for prolactin-induced Rac1 activation; kinase-inactive Nek3 blocks Rac1 activation but does not affect VAV2-potentiated STAT5-mediated gene expression, indicating pathway bifurcation. Yeast two-hybrid, co-immunoprecipitation, Nek3 kinase assay, siRNA/dominant-negative of Nek3, Rac1 activation assay (CHO transfectants) Molecular endocrinology Medium 15618286
2011 ADIP scaffold protein interacts with VAV2 in a Src phosphorylation-dependent manner and mediates PDGF-induced Rac activation; knockdown of ADIP or afadin inhibits Rac activation; ADIP localizes at the leading edge during PDGF-induced cell movement. Co-immunoprecipitation, siRNA knockdown of ADIP/afadin, Rac activation assay, cell migration assay The Journal of biological chemistry Medium 22027834
2011 TGFβ rapidly activates RhoA/RhoB via a Smad2/3-independent mechanism involving Src activation followed by VAV2 activation; Src inhibitor PP2 or VAV2 siRNA blocks early TGFβ-induced RhoA activation. Smad2 siRNA, TβRI inhibitor, Src inhibitor PP2, VAV2 siRNA, RhoA activation assay Cellular physiology and biochemistry Medium 21865730
2011 Campylobacter jejuni invasion requires VAV2 as a linker between activated EGFR/PDGFR/PI3K and Cdc42 activation; VAV2 siRNA and Vav1/2-knockout cells show impaired Cdc42 activation and reduced bacterial invasion; signaling cascade is fibronectin→integrin-β1→FAK/Src→EGFR/PDGFR→PI3K→Vav2→Cdc42. siRNA, Vav1/2 double-knockout cells, dominant-negative constructs, Cdc42-GTP pull-down, gentamicin protection invasion assay, pharmacological inhibitors Cell communication and signaling Medium 22204307
2012 Wnt3a-induced Rac1 activation requires p120-catenin binding to both Rac1 and VAV2; Wnt3a promotes release of p120-catenin from E-cadherin (via CK1-mediated serine phosphorylation and Src/Fyn-inhibited tyrosine phosphorylation) enabling p120-catenin-Vav2-Rac1 complex formation; p120-catenin mutants deficient in Vav2 or Rac1 binding fail to rescue p120-catenin depletion phenotype in Xenopus gastrulation. Co-immunoprecipitation, Rac1 activity assay, p120-catenin point mutants, Xenopus embryo rescue assay, kinase inhibitors Journal of cell science Medium 22946057
2012 NMR solution structure of VAV2 SH2 domain determined in free form and in complex with phosphotyrosine peptide pY1408 from Arap3; VAV2 SH2 domain directly binds phosphorylated Y1403 and Y1408 within the C-terminal region of Arap3 (Kd ~0.27 and ~1.40 μM); Phe in the BG loop determines pY+3 specificity of VAV2 SH2 domain; interaction confirmed in vitro (ITC) and in vivo (co-IP). NMR structure determination, ITC, NMR chemical shift perturbation, co-immunoprecipitation Journal of structural biology High 22750419
2013 Paxillin kinase linker (PKL/GIT2) interacts with VAV2 in a phosphorylation-dependent manner and is required for VAV2 activation downstream of integrin engagement and EGF stimulation; in turn, VAV2 regulates redistribution of PKL and β-PIX to focal adhesions; VAV2 knockdown decreases directional persistence and polarization in migrating cells. Co-immunoprecipitation, siRNA knockdown of PKL and VAV2, GTPase activity assays, cell migration directionality assays Molecular biology of the cell Medium 23615439
2014 Vimentin forms a complex with VAV2 and FAK at focal adhesions; vimentin depletion reduces VAV2 pY142 phosphorylation and downstream pY397-FAK activity; vimentin is required for maintaining VAV2-mediated Rac1 activation; constitutively active Rac1 rescues FAK activity and cell adhesion defects caused by vimentin or VAV2 depletion. Phosphoproteomics screen, co-immunoprecipitation, siRNA knockdown, constitutively active Rac1 rescue, FAK and VAV2 phosphorylation assays Oncogene Medium 24858039
2014 EphA receptors signal via VAV2 to activate RhoA mediating prostate cancer cell-cell repulsion; both VAV2 and RhoA are required for EphA-mediated contact repulsion; in EphA2/EphA4 or VAV2 siRNA-treated cells, contact repulsion is restored by partial microtubule destabilization. siRNA knockdown of EphA2/EphA4, Vav2, RhoA; 2D dispersal and 3D spheroid assays; RhoA activation assay Biology open Medium 24795148
2014 SF-1 transcription factor directly regulates VAV2 gene transcription in adrenocortical carcinoma cells; increased SF-1 abundance drives increased VAV2 expression, which is a critical factor for SF-1-induced cytoskeletal remodeling and invasion in vitro (Matrigel) and in vivo (chicken chorioallantoic membrane model). SF-1/VAV2 manipulation (overexpression and knockdown), invasion assays (Matrigel and CAM), transcriptional reporter analysis Science signaling Medium 28270555
2014 Genetic manipulation of Rac1 specifically in vascular smooth muscle cells (via Cre-loxP): active VAV2 expression in vSMCs causes hypotension and abolishes systemic Vav2-KO-induced hypertension; Rac1-specific deletion in vSMCs causes defective nitric oxide vasodilation and hypertension; Rac1 (but not VAV2) is additionally required for neointima formation. Inducible Cre-loxP genetic mouse models, blood pressure measurements, vascular pharmacological assays, neointima formation assays Molecular and cellular biology High 25288640
2015 VAV2 is required for GDNF/Ret-mediated regulation of dopamine transporter (DAT) cell surface expression and activity in the nucleus accumbens; Vav2-deficient mice display elevated DAT activity and increased intracellular DA; Vav2-KO mice show reduced DAT activity and diminished cocaine behavioral response after cocaine exposure. Vav2 knockout mice, Ret knockout mice, DAT activity assays, DAT surface expression assays, cocaine behavioral assay Nature neuroscience High 26147533
2015 VAV2 is a GEF for Rac1 in pancreatic beta cells; VAV2 siRNA or the VAV2-Rac1 interaction inhibitor Ehop-016 attenuates glucose-induced Rac1 activation, cortical actin remodeling, and glucose-stimulated insulin secretion (GSIS); high glucose promotes co-localization of Rac1 and VAV2. siRNA knockdown, pharmacological inhibitor (Ehop-016), G-LISA Rac1 activation assay, live cell actin imaging (LifeAct-GFP), insulin secretion assay, confocal microscopy Diabetologia Medium 26224100
2016 MST3 kinase interacts with VAV2 via its proline-rich region (353KDIPKRP359) binding to the SH3 domain of VAV2; MST3 increases VAV2 phosphorylation and GTP-Rac1 levels; this interaction is required for MST3-mediated proliferation promotion; mutation of the two prolines in the MST3 proline-rich domain abolishes VAV2 interaction and MST3-dependent proliferation. Co-immunoprecipitation, domain mapping with MST3 truncation mutants, co-localization (confocal), Rac1-GTP assay, proliferation assay, MST3 knockdown Oncotarget Medium 26910843
2016 Crystal structure of VAV2 SH2 domain in complex with TXNIP phosphotyrosine PPxY peptide determined; tyrosine-phosphorylated PPxY motifs bind to VAV2 SH2 domain with Kd ~10 μM; phosphorylation is indispensable for this interaction; conserved recognition mechanism revealed. Crystal structure determination, Kd measurement (binding assay) FEBS letters High 26919541
2017 Phosphorylated cortactin (at Y421 and Y466 but not Y482) recruits VAV2 via its SH2 domain to invadopodia; the Vav2 SH2 domain is required for VAV2 invadopodial localization and efficient matrix degradation; VAV2 promotes Rac3 activation at invadopodia; Rac3 knockdown reduces matrix degradation, and constitutively active Rac3 rescues VAV2-knockdown deficits. SH2 domain binding screen, phosphopeptide binding assays, SH2 domain mutant expression, siRNA knockdown, matrix degradation assay, Rac3 biosensor (FRET), Rac3 activation assay Molecular biology of the cell High 28356423
2020 VAV2 catalytic activity is required for neurite outgrowth promotion; Vav2 inhibits T cell receptor-induced Ca2+ entry via its GEF activity toward Cdc42 (not Rac1); in vivo GEF-trapping assay demonstrates Cdc42 (but not Rac1) interacts with the catalytic surface of Vav2; Vav1 discriminates Cdc42 from Rac1 via F56 (absent in Vav2); Cdc42-specific inhibitor or Cdc42 shRNA prevents Vav2-mediated suppression of TCR-induced Ca2+ entry. In vivo GEF-trapping assay in intact cells, shRNA, Cdc42-specific inhibitor ZCL278, mutagenesis (Vav1 F56W), Ca2+ entry measurement Journal of cell science Medium 31974114
2020 VAV2 catalytic activity modulates IGF1- and insulin-stimulated PI3K signaling in skeletal muscle; mice with decreased VAV2 catalytic activity exhibit reduced muscle mass and impaired insulin responsiveness; mice with hyperactive VAV2 show muscle hypertrophy and increased insulin responsiveness; hypoactive VAV2 predisposes to and hyperactive VAV2 protects against high-fat diet-induced metabolic imbalance. Knock-in mice with hypo- or hyperactive Vav2 (catalytic activity mutants), insulin/IGF1 signaling assays, metabolic measurements, muscle mass analysis Nature communications High 33199701
2020 VAV2 catalytic activity drives regenerative proliferation and poor differentiation in keratinocytes and hnSCC cells via c-Myc- and YAP/TAZ-dependent transcriptional programs; this function requires both RHO GTPase catalysis and specific downstream transcriptome programs. VAV2 overexpression/knockdown in keratinocytes and patient-derived hnSCC cells, catalysis-dead mutants, c-Myc and YAP/TAZ pathway analysis, transcriptomic analysis Nature communications Medium 32963234
2020 VAV2 SH2 domain binds PI(4,5)P2 and PI(3,4,5)P3 lipids specifically (millimolar affinity); NMR identifies the lipid-binding site; VAV2 SH2 domain binds the phosphorylated juxtamembrane region of EphA2 (pY594) in solution and on lipid membrane nanodiscs; membrane environment modulates VAV2-SH2/EphA2 interaction. NMR chemical shift perturbation, ITC, peptide-based lipid nanodisc system for membrane-context binding The Biochemical journal High 32897354
2021 VAV2 is required for Ku70/Ku80 complex formation and participates in non-homologous end joining (NHEJ) repair of DNA damage caused by ionizing radiation; VAV2 overexpression upregulates STAT1; STAT1 inhibition by Fludarabine promotes radiosensitivity of VAV2-overexpressing radioresistant cancer xenografts. VAV2 knockdown/overexpression, co-immunoprecipitation of Ku70/Ku80, DNA damage repair assays, in vivo xenograft radiotherapy experiments with Fludarabine Signal transduction and targeted therapy Medium 34462423
2022 VAV2 is a novel interaction partner of APP; VAV2 SH2 domain directly binds pY682 in the intracellular tail of APP (ITC and NMR); crystal structure of VAV2-SH2/APP phosphopeptide complex determined; full-length VAV2-APP interaction confirmed by co-IP and GST pull-down in cells; VAV2 overexpression inhibits APP degradation and increases APP protein level in a SH2 domain-dependent manner. ITC, NMR titration, crystal structure determination, co-immunoprecipitation, GST pull-down, immunofluorescence, APP level measurement Scientific reports High 35882892
2022 In CD16+ fibroblasts, trastuzumab-CD16 interaction activates the SYK-VAV2-RhoA-ROCK-MLC2-MRTF-A pathway, leading to elevated contractile force and extracellular matrix production (desmoplasia); VAV2 is indispensable for CD16 function in fibroblasts (but not in leukocytes); targeting VAV2 reverses CD16+ fibroblast-mediated desmoplasia. siRNA/inhibitor targeting of pathway components, contractile force assays, ECM production measurement, VAV2 inhibition in fibroblast vs leukocyte comparison Cancer cell Medium 36379207
2024 VAV2 regulates ribosome biogenesis in keratinocytes and OSCC cells in a catalysis-dependent manner via RAC1/RHOA GTPases → PAK/ROCK family kinases → c-MYC and YAP/TAZ transcription factors → RNA Polymerase I activity and 47S pre-rRNA synthesis; RNA Pol I inhibition is a therapeutic vulnerability for cells with high VAV2 catalytic activity. Catalysis-dead VAV2 mutants, RNA Pol I activity assays, pre-rRNA quantification, pharmacological inhibition, patient-derived cell line experiments Scientific reports Medium 38374399
2025 VAV2 overexpression promotes prostate cancer proliferation and metastasis by activating the PAK1/AKT signaling pathway through PAK1 phosphorylation; VAV2 contributes to enzalutamide resistance by recruiting the deubiquitinase USP48 to enhance AR/ARv7 protein stability via reduced ubiquitination. Functional overexpression/knockdown, PAK1 phosphorylation assay, co-immunoprecipitation of USP48, ubiquitination assay, AR/ARv7 stability measurement International journal of biological sciences Medium 40303312
2025 EGFR-VAV2 signaling is sustained in endosomes; endogenous VAV2 is co-endocytosed with EGFR; chemotactic migration toward EGF requires both VAV2 and clathrin-mediated endocytosis; sustained Rac1 activation (a VAV2 substrate) also depends on clathrin; endogenous Rac1 localizes to EGFR-containing endosomes. Live-cell microscopy of genome-edited fluorescently-tagged VAV2 and Rac1, clathrin inhibition, VAV2 siRNA knockdown, Rac1 activation assay, chemotaxis assay Journal of cell science Medium 39744818

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Analysis of receptor signaling pathways by mass spectrometry: identification of vav-2 as a substrate of the epidermal and platelet-derived growth factor receptors. Proceedings of the National Academy of Sciences of the United States of America 341 10618391
1998 Phosphorylation-dependent and constitutive activation of Rho proteins by wild-type and oncogenic Vav-2. The EMBO journal 230 9822605
2000 Vav2 is an activator of Cdc42, Rac1, and RhoA. The Journal of biological chemistry 228 10744696
2013 MicroRNA-195 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting the expression of VEGF, VAV2, and CDC42. Hepatology (Baltimore, Md.) 190 23468064
2000 Vav2 activates Rac1, Cdc42, and RhoA downstream from growth factor receptors but not beta1 integrins. Molecular and cellular biology 183 10982832
2001 Hyaluronan promotes CD44v3-Vav2 interaction with Grb2-p185(HER2) and induces Rac1 and Ras signaling during ovarian tumor cell migration and growth. The Journal of biological chemistry 167 11606575
2003 Rac1 function is required for Src-induced transformation. Evidence of a role for Tiam1 and Vav2 in Rac activation by Src. The Journal of biological chemistry 148 12810717
2001 Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation. Nature immunology 145 11376342
2007 VEGF-induced Rac1 activation in endothelial cells is regulated by the guanine nucleotide exchange factor Vav2. Experimental cell research 140 17686471
2001 Compensation between Vav-1 and Vav-2 in B cell development and antigen receptor signaling. Nature immunology 136 11376343
1996 Isolation and characterization of murine vav2, a member of the vav family of proto-oncogenes. Oncogene 132 8710375
2014 Vimentin regulates lung cancer cell adhesion through a VAV2-Rac1 pathway to control focal adhesion kinase activity. Oncogene 125 24858039
2005 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. Molecular biology of the cell 124 15728722
2002 Mechanism of epidermal growth factor regulation of Vav2, a guanine nucleotide exchange factor for Rac. The Journal of biological chemistry 99 12454019
2012 The rho exchange factors vav2 and vav3 control a lung metastasis-specific transcriptional program in breast cancer cells. Science signaling 96 23033540
2001 Vav2 is required for cell spreading. The Journal of cell biology 90 11448999
2018 Integrin α5 down-regulation by miR-205 suppresses triple negative breast cancer stemness and metastasis by inhibiting the Src/Vav2/Rac1 pathway. Cancer letters 85 29964204
2004 Vav2 as a Rac-GDP/GTP exchange factor responsible for the nectin-induced, c-Src- and Cdc42-mediated activation of Rac. The Journal of biological chemistry 80 15485841
2003 EGF receptor mediates adhesion-dependent activation of the Rac GTPase: a role for phosphatidylinositol 3-kinase and Vav2. Oncogene 80 12955089
1995 Identification of VAV2 on 9q34 and its exclusion as the tuberous sclerosis gene TSC1. Annals of human genetics 79 7762982
2007 Persistent activation of Rac1 in squamous carcinomas of the head and neck: evidence for an EGFR/Vav2 signaling axis involved in cell invasion. Carcinogenesis 76 17234718
2010 Filamin B plays a key role in vascular endothelial growth factor-induced endothelial cell motility through its interaction with Rac-1 and Vav-2. The Journal of biological chemistry 74 20110358
2006 Activation of Rac by cadherin through the c-Src-Rap1-phosphatidylinositol 3-kinase-Vav2 pathway. Oncogene 68 16170364
2006 CD47 promotes neuronal development through Src- and FRG/Vav2-mediated activation of Rac and Cdc42. The Journal of neuroscience : the official journal of the Society for Neuroscience 68 17135401
2014 Diosgenin inhibits the migration of human breast cancer MDA-MB-231 cells by suppressing Vav2 activity. Phytomedicine : international journal of phytotherapy and phytopharmacology 67 24656238
2000 Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes. The EMBO journal 66 11080163
2004 Novel association of Vav2 and Nek3 modulates signaling through the human prolactin receptor. Molecular endocrinology (Baltimore, Md.) 61 15618286
2009 The Rho/Rac exchange factor Vav2 controls nitric oxide-dependent responses in mouse vascular smooth muscle cells. The Journal of clinical investigation 58 20038798
2011 The signaling pathway of Campylobacter jejuni-induced Cdc42 activation: Role of fibronectin, integrin beta1, tyrosine kinases and guanine exchange factor Vav2. Cell communication and signaling : CCS 56 22204307
2008 Contribution of guanine nucleotide exchange factor Vav2 to hyperhomocysteinemic glomerulosclerosis in rats. Hypertension (Dallas, Tex. : 1979) 56 19029489
2007 Loss of Vav2 proto-oncogene causes tachycardia and cardiovascular disease in mice. Molecular biology of the cell 56 17202406
2006 PTP-PEST couples membrane protrusion and tail retraction via VAV2 and p190RhoGAP. The Journal of biological chemistry 56 16513648
2010 Astrocyte-produced ephrins inhibit schwann cell migration via VAV2 signaling. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 20335460
2022 CD16+ fibroblasts foster a trastuzumab-refractory microenvironment that is reversed by VAV2 inhibition. Cancer cell 52 36379207
2019 MicroRNA-331-3p inhibits epithelial-mesenchymal transition by targeting ErbB2 and VAV2 through the Rac1/PAK1/β-catenin axis in non-small-cell lung cancer. Cancer science 51 30955235
2010 Evidence for VAV2 and ZNF433 as susceptibility genes for multiple sclerosis. Journal of neuroimmunology 51 20598377
2010 VAV2 and VAV3 as candidate disease genes for spontaneous glaucoma in mice and humans. PloS one 49 20140222
2002 Vav1, but not Vav2, contributes to platelet aggregation by CRP and thrombin, but neither is required for regulation of phospholipase C. Blood 47 12411320
2000 The Rho family guanine nucleotide exchange factor Vav-2 regulates the development of cell-mediated cytotoxicity. The Journal of experimental medicine 46 10934226
2018 Mesenchymal stem cells promote endothelial progenitor cell migration, vascularization, and bone repair in tissue-engineered constructs via activating CXCR2-Src-PKL/Vav2-Rac1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 43 29229683
2010 Negative regulation of EGFR-Vav2 signaling axis by Cbl ubiquitin ligase controls EGF receptor-mediated epithelial cell adherens junction dynamics and cell migration. The Journal of biological chemistry 41 20940296
2017 Phosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in invasive breast cancer cells. Molecular biology of the cell 40 28356423
2005 Recognition and activation of Rho GTPases by Vav1 and Vav2 guanine nucleotide exchange factors. Biochemistry 40 15850391
2002 Critical but distinct roles for the pleckstrin homology and cysteine-rich domains as positive modulators of Vav2 signaling and transformation. Molecular and cellular biology 38 11909943
2017 Dosage-dependent regulation of VAV2 expression by steroidogenic factor-1 drives adrenocortical carcinoma cell invasion. Science signaling 37 28270555
2015 Identification of a Vav2-dependent mechanism for GDNF/Ret control of mesolimbic DAT trafficking. Nature neuroscience 37 26147533
2014 EphA receptors regulate prostate cancer cell dissemination through Vav2-RhoA mediated cell-cell repulsion. Biology open 37 24795148
2021 VAV2 is required for DNA repair and implicated in cancer radiotherapy resistance. Signal transduction and targeted therapy 36 34462423
2016 MST3 promotes proliferation and tumorigenicity through the VAV2/Rac1 signal axis in breast cancer. Oncotarget 36 26910843
2010 VAV2 regulates epidermal growth factor receptor endocytosis and degradation. Oncogene 36 20140013
2015 VAV2, a guanine nucleotide exchange factor for Rac1, regulates glucose-stimulated insulin secretion in pancreatic beta cells. Diabetologia 35 26224100
2009 Host deficiency in Vav2/3 guanine nucleotide exchange factors impairs tumor growth, survival, and angiogenesis in vivo. Molecular cancer research : MCR 35 19435813
2020 VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma. Nature communications 34 32963234
2017 Autocrine VEGF and IL-8 Promote Migration via Src/Vav2/Rac1/PAK1 Signaling in Human Umbilical Vein Endothelial Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 34 28278510
2012 Upon Wnt stimulation, Rac1 activation requires Rac1 and Vav2 binding to p120-catenin. Journal of cell science 34 22946057
2010 Variations in NTF4, VAV2, and VAV3 genes are not involved with primary open-angle and primary angle-closure glaucomas in an indian population. Investigative ophthalmology & visual science 34 20463313
2005 Vav1 and Vav2 play different roles in macrophage migration and cytoskeletal organization. Experimental cell research 34 16137676
2010 Tyrosine-phosphorylated caveolin-1 blocks bacterial uptake by inducing Vav2-RhoA-mediated cytoskeletal rearrangements. PLoS biology 32 20808760
2017 Tiam1/Vav2-Rac1 axis: A tug-of-war between islet function and dysfunction. Biochemical pharmacology 30 28202288
2020 Vav2 catalysis-dependent pathways contribute to skeletal muscle growth and metabolic homeostasis. Nature communications 29 33199701
2004 Adhesion molecule L1 stimulates neuronal migration through Vav2-Pak1 signaling. Neuroreport 28 15597056
2009 Mechanical stretch-induced RhoA activation is mediated by the RhoGEF Vav2 in mesangial cells. Cellular signalling 27 19755152
2007 Mechanism of homocysteine-induced Rac1/NADPH oxidase activation in mesangial cells: role of guanine nucleotide exchange factor Vav2. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 27 17982273
2009 Distinct roles for Rho versus Rac/Cdc42 GTPases downstream of Vav2 in regulating mammary epithelial acinar architecture. The Journal of biological chemistry 25 19826000
2001 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. The Journal of biological chemistry 25 11262396
2017 Contribution of guanine nucleotide exchange factor Vav2 to NLRP3 inflammasome activation in mouse podocytes during hyperhomocysteinemia. Free radical biology & medicine 24 28193546
2010 Balanced Vav2 GEF activity regulates neurite outgrowth and branching in vitro and in vivo. Molecular and cellular neurosciences 24 20298788
2016 EphB3 Stimulates Cell Migration and Metastasis in a Kinase-dependent Manner through Vav2-Rho GTPase Axis in Papillary Thyroid Cancer. The Journal of biological chemistry 23 27986811
2007 Activated Vav2 modulates cellular invasion through Rac1 and Cdc42 in oral squamous cell carcinoma. Oral oncology 23 17996485
2014 Genetic dissection of the vav2-rac1 signaling axis in vascular smooth muscle cells. Molecular and cellular biology 21 25288640
2011 TGFβ-induced early activation of the small GTPase RhoA is Smad2/3-independent and involves Src and the guanine nucleotide exchange factor Vav2. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 21865730
2011 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. The Journal of biological chemistry 21 22027834
2023 AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway. Journal of translational medicine 19 36631800
2022 Tumor-Derived Exosome FGD5-AS1 Promotes Angiogenesis, Vascular Permeability, and Metastasis in Thyroid Cancer by Targeting the miR-6838-5p/VAV2 Axis. Journal of oncology 19 35528244
2020 SNHG3 silencing suppresses the malignant development of triple-negative breast cancer cells by regulating miRNA-326/integrin α5 axis and inactivating Vav2/Rac1 signaling pathway. European review for medical and pharmacological sciences 19 32495883
2001 Membrane-targeting is critical for the phosphorylation of Vav2 by activated EGF receptor. Cellular signalling 19 11516622
2021 Helicobacter pylori CagA Induces Cortactin Y-470 Phosphorylation-Dependent Gastric Epithelial Cell Scattering via Abl, Vav2 and Rac1 Activation. Cancers 17 34439396
2008 Collagen phagocytosis is regulated by the guanine nucleotide exchange factor Vav2. American journal of physiology. Cell physiology 17 18434624
2005 Cholecystokinin stimulates the recruitment of the Src-RhoA-phosphoinositide 3-kinase pathway by Vav-2 downstream of G(alpha13) in pancreatic acini. Biochemical and biophysical research communications 17 16297869
2014 Vav2 protein overexpression marks and may predict the aggressive subtype of ductal carcinoma in situ. Biomarker research 16 25785189
2022 The tRNA-Cys-GCA Derived tsRNAs Suppress Tumor Progression of Gliomas via Regulating VAV2. Disease markers 15 36426134
2024 Columbianadin ameliorates rheumatoid arthritis by attenuating synoviocyte hyperplasia through targeted vimentin to inhibit the VAV2/Rac-1 signaling pathway. Journal of advanced research 13 39369957
2018 Ubiquitin E3 Ligase MARCH7 promotes proliferation and invasion of cervical cancer cells through VAV2-RAC1-CDC42 pathway. Oncology letters 13 30008934
2017 Upregulated Vav2 in gastric cancer tissues promotes tumor invasion and metastasis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 13 28459214
2007 Strongly reduced alloreactivity and long-term survival times of cardiac allografts in Vav1- and Vav1/Vav2-knockout mice. Transplant international : official journal of the European Society for Organ Transplantation 12 17326776
2013 Paxillin kinase linker (PKL) regulates Vav2 signaling during cell spreading and migration. Molecular biology of the cell 10 23615439
2012 Identification and structural basis for a novel interaction between Vav2 and Arap3. Journal of structural biology 10 22750419
2008 Therapeutic IMC-C225 antibody inhibits breast cancer cell invasiveness via Vav2-dependent activation of RhoA GTPase. Clinical cancer research : an official journal of the American Association for Cancer Research 10 18829495
2021 Genetic variants of DOCK2, EPHB1 and VAV2 in the natural killer cell-related pathway are associated with non-small cell lung cancer survival. American journal of cancer research 9 34094683
2020 Vav2 lacks Ca2+ entry-promoting scaffolding functions unique to Vav1 and inhibits T cell activation via Cdc42. Journal of cell science 8 31974114
2016 Structural basis for a novel interaction between TXNIP and Vav2. FEBS letters 8 26919541
2025 VAV2 exists in extrachromosomal circular DNA and contributes Enzalutamide resistance of prostate cancer via stabilization of AR/ARv7. International journal of biological sciences 7 40303312
2020 Biochemical and NMR characterization of the interactions of Vav2-SH2 domain with lipids and the EphA2 juxtamembrane region on membrane. The Biochemical journal 7 32897354
2013 Molecular genetic analysis of primary open-angle glaucoma, normal tension glaucoma, and developmental glaucoma for the VAV2 and VAV3 gene variants in Japanese subjects. Biochemical and biophysical research communications 7 23402756
2022 Vav2 is a novel APP-interacting protein that regulates APP protein level. Scientific reports 6 35882892
2022 Potentially functional genetic variants of VAV2 and PSMA4 in the immune-activation pathway and non-small cell lung cancer survival. The journal of gene medicine 6 36039727
2013 Potassium-chloride cotransporter 3 interacts with Vav2 to synchronize the cell volume decrease response with cell protrusion dynamics. PloS one 6 23724134
2025 Cell migration signaling through the EGFR-VAV2-Rac1 pathway is sustained in endosomes. Journal of cell science 5 39744818
2022 The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function. Oncogene 5 35534539
2024 VAV2 orchestrates the interplay between regenerative proliferation and ribogenesis in both keratinocytes and oral squamous cell carcinoma. Scientific reports 4 38374399

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