Affinage

VAV1

Proto-oncogene vav · UniProt P15498

Length
845 aa
Mass
98.3 kDa
Annotated
2026-06-11
100 papers in source corpus 48 papers cited in narrative 48 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VAV1 is a hematopoietic guanine nucleotide exchange factor that couples immune-receptor engagement to Rho-family GTPase activation, cytoskeletal remodeling, and transcriptional programs, and is essential for lymphocyte development and antigen-receptor responses (PMID:8994827, PMID:14623913). It is a substrate of receptor- and TCR-associated tyrosine kinases—including Lck, Fyn, and JAK2—and its activity rises in parallel with its tyrosine phosphorylation upon receptor triggering (PMID:8484124, PMID:11005864, PMID:9162069). Phosphorylation of the acidic-region tyrosine Tyr174, together with neighboring tyrosines that conform to SH2-binding motifs and engage Lck, PI3K p85, and PLCγ, relieves autoinhibition and sustains TCR-signaling microclusters (PMID:17050525). Catalytically, the cysteine-rich domain (CRD) forms an intramolecular network with the DH domain C-terminal helix that stabilizes the catalytic core against the Rac1 Switch II region to displace nucleotide and governs both binding and the rate-limiting exchange step (PMID:18589439, PMID:15850391). Once activated, VAV1 generates GTP-loaded Rac, Rho, and Cdc42 to drive actin polymerization, integrin clustering and inside-out LFA-1 activation, MTOC/granule polarization in cytotoxic lymphocytes, and phagocytosis (PMID:8994827, PMID:11911819, PMID:12616499, PMID:16546099, PMID:9687532). VAV1 is recruited to SLP-76 microclusters at the immunological synapse through its C-terminal SH2 and SH3(B) domains binding SLP-76 phosphotyrosines 112 and 128, both as a catalytic GEF and as a GEF-independent scaffold (PMID:21386095, PMID:22956543, PMID:8673706). Downstream, it controls Ca2+/NFAT signaling via PLCγ and LAT phosphorylation (PMID:11340169, PMID:14764585), ERK activation by recruiting RasGRP1 and Sos1/2 (PMID:14764585), NF-κB through IKKα and a Rac–PKCθ pathway (PMID:12626540, PMID:10714681), and a PI3K/Akt/FOXO1 axis governing cell-cycle progression (PMID:17015685). VAV1 additionally translocates to the nucleus, where it is an integral component of NFAT- and NF-κB-like transcription complexes (PMID:11994417), and it is negatively regulated by Cbl-mediated ubiquitinylation that degrades the phosphorylated protein (PMID:12881521). Aberrant VAV1—ectopic expression in pancreatic carcinoma and recurrent mutations, deletions, and fusions in peripheral T cell lymphomas—acts as an oncogenic driver by augmenting catalytic and scaffolding effector pathways (PMID:15652748, PMID:28832024, PMID:28062691).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1992 High

    Established VAV1 as an SH2-containing tyrosine-kinase substrate linking receptor activation to signaling and identified its oncogenic potential, framing the central question of how phosphorylation controls its activity.

    Evidence Co-IP with activated EGF/PDGF receptors and TCR/CD4 co-activation phosphorylation, plus oncogenic activation by HLH-motif deletion in NIH3T3 and T cells

    PMID:1311423

    Open questions at the time
    • Did not define the catalytic enzymatic activity
    • Mechanism of phosphorylation-dependent activation unresolved
  2. 1993 High

    Showed VAV1 immunoprecipitates carry nucleotide-releasing activity for Ras-related GTPases that rises with TCR-triggered phosphorylation, first connecting receptor signaling to GEF function.

    Evidence GRF activity assays on Vav immunoprecipitates with PTK-inhibitor controls and in vitro Lck kinase assay

    PMID:8484124

    Open questions at the time
    • Specific GTPase substrates not defined
    • Activity from immunoprecipitates, not purified protein
  3. 1996 High

    Defined VAV1 as a direct upstream GEF for Rho-family GTPases driving actin polymerization and JNK signaling, establishing the cytoskeletal effector arm.

    Evidence Microinjection into Swiss 3T3 fibroblasts with actin staining, Rho/Rac/Cdc42 activation and SAPK/JNK1 assays

    PMID:8994827

    Open questions at the time
    • Did not resolve domain basis of catalytic activation
    • Tested in fibroblasts rather than native hematopoietic cells
  4. 1996 High

    Identified the SH2-dependent VAV1–SLP-76 interaction required for VAV1 phosphorylation and synergistic NF-AT/IL-2 activation, anchoring VAV1 in the TCR signalosome.

    Evidence Co-IP, SH2 mutants, and NF-AT/IL-2 reporter assays in Jurkat cells

    PMID:8673706

    Open questions at the time
    • Did not map the SLP-76 phosphosites engaged
    • Scaffolding versus catalytic contributions not separated
  5. 1995 High

    Genetic ablation established VAV1 as essential for antigen-receptor-induced proliferation, thymocyte positive selection, and lymphocyte development.

    Evidence RAG-complementation knockout ES cells, proliferation assays, and flow-cytometric thymic analysis

    PMID:7700358 PMID:7700360

    Open questions at the time
    • Did not distinguish which downstream pathway accounts for the developmental defect
    • Compensation by paralogs not assessed
  6. 1998 High

    Defined the VAV1-dependent TCR effector branch—Ca2+ flux, actin/TCR clustering, NFATc1, IL-2, and cell-cycle entry—and its association with cytoskeletal anchors, separating it from MAPK/JNK in T cells.

    Evidence Vav1-/- mice with Ca2+, actin, cell-cycle assays and Co-IP of talin/vinculin/SLP-76

    PMID:9601639

    Open questions at the time
    • Did not establish whether Ca2+ defect is catalytic or scaffolding
    • MAPK independence in T cells later revised by combinatorial knockouts
  7. 1998 Medium

    Extended VAV1–Rac signaling to NK-cell killing, linking GEF activity to granule polarization and conjugate formation.

    Evidence NK cytotoxicity assays with WT and exchange-dead Vav and dominant-negative Rac1

    PMID:9687532

    Open questions at the time
    • Single lab; overexpression-based
    • Receptor coupling to Vav not defined
  8. 2001 High

    Reconstitution showed VAV1 acts directly upstream of PLCγ for FcεRI-driven calcium mobilization in mast cells, generalizing its role across immunoreceptors.

    Evidence Vav1-/- mast cell reconstitution with PLCγ phosphorylation and Ca2+ assays

    PMID:11340169

    Open questions at the time
    • Mechanism by which Vav1 promotes PLCγ phosphorylation not resolved here
    • Catalytic requirement not tested with GEF-dead mutant
  9. 2002 Medium

    Demonstrated a nuclear, transcription-complex role for VAV1 dependent on its C-terminal SH3 domain, establishing a function beyond cytoplasmic GEF signaling.

    Evidence Subcellular fractionation, imaging, and chromatin Co-IP with NFAT/NF-κB complexes using domain mutants

    PMID:11994417

    Open questions at the time
    • Direct DNA or transcription-factor contacts not defined
    • Single lab
  10. 2002 High

    Resolved that VAV1 controls integrin clustering and inside-out LFA-1 activation and MTOC polarization, distinct from synapse protein organization, defining its adhesion role.

    Evidence Vav1-/- thymocytes with adhesion, LFA-1 activation, conjugate and MTOC polarization assays, WASP comparison

    PMID:11911819 PMID:12616499

    Open questions at the time
    • GTPase mediating integrin activation not fully defined here
    • Inside-out signaling intermediates unmapped
  11. 2003 High

    Combinatorial Vav1/2/3 knockouts proved the family is essential for lymphocyte development and antigen-receptor Ca2+ signaling and revealed lineage-specific MAPK dependence and paralog redundancy.

    Evidence Triple knockout mice with flow cytometry, Ca2+ flux, and MAPK assays

    PMID:14623913

    Open questions at the time
    • Did not isolate unique non-redundant Vav1 functions in all settings
    • Molecular basis of B- versus T-cell MAPK difference unresolved
  12. 2003 High

    Mapped the VAV1-to-ERK route via LAT phosphorylation controlling RasGRP1 (through PLCγ) and Sos1/2 recruitment, and the VAV1–IKKα/PKCθ route to NF-κB, defining parallel transcriptional effector arms.

    Evidence Vav1-/- thymocytes with ERK/Ras and membrane-recruitment assays; Co-IP and kinase assays of Vav1–IKKα; PKCθ translocation/kinase assays

    PMID:10714681 PMID:12626540 PMID:14764585

    Open questions at the time
    • Whether LAT phosphorylation control is direct or cytoskeleton-dependent unresolved
    • Quantitative contribution of each arm to outcomes not weighted
  13. 2003 Medium

    Identified Cbl-mediated ubiquitinylation as the negative regulatory mechanism degrading phosphorylated VAV1, closing the activation loop.

    Evidence Cbl-/- T cells and 293T ubiquitin assays with RING-finger mutant controls

    PMID:12881521

    Open questions at the time
    • Degradation route (proteasomal/lysosomal) and kinetics not detailed
    • Single lab
  14. 2005 High

    Kinetic and NMR analyses established that the CRD actively participates in both Rac1 binding and the rate-limiting exchange step, mechanistically defining the catalytic cycle.

    Evidence In vitro GEF kinetics, fluorescence anisotropy, NMR chemical shift mapping, and mutagenesis

    PMID:15850391

    Open questions at the time
    • Did not provide a full-length autoinhibited structure
    • Phosphorylation-coupled conformational change not directly observed
  15. 2005 Medium

    Connected VAV1 to chemokine and growth-factor receptor inputs—CXCL12-driven integrin adhesion/migration, EPO/PI3K proliferation—and to PI3K/Akt/FOXO1 control of cell-cycle progression, broadening its receptor coupling.

    Evidence siRNA/dominant-negative Vav1 with Rac and adhesion/migration assays; p85 Co-IP and JAK2 kinase assay; Akt/FOXO1/14-3-3 and cell-cycle assays in Vav1-/- T cells

    PMID:15872091 PMID:17015685 PMID:9162069

    Open questions at the time
    • Direct versus indirect coupling to PI3K/Akt not fully resolved
    • Several findings single-lab
  16. 2006 High

    Defined receptor-selective VAV1 requirements in innate effectors: DAP10/NKG2D cytotoxicity via a Grb2-VAV1 intermediate, and integrin-receptor (but not FcγR) phagocytosis via Rac-driven Arp2/3 actin assembly.

    Evidence Combinatorial knockout NK cells and macrophages, Co-IP of DAP10-Grb2-Vav1, cytotoxicity/phagocytosis assays, constitutively active Rac rescue

    PMID:16546099 PMID:16582911 PMID:16887996

    Open questions at the time
    • Basis of ITAM versus DAP10 selectivity not fully defined
    • Quantitative GTPase requirements across receptors unmapped
  17. 2008 High

    The DH-PH-CRD–Rac1 crystal structure revealed the CRD–DH intramolecular network that stabilizes the catalytic core for Switch-II engagement and nucleotide displacement, providing the structural basis of catalysis and substrate breadth.

    Evidence X-ray crystallography at 2.6 Å, SAXS, and mutagenesis with GEF assays

    PMID:18589439

    Open questions at the time
    • Did not capture the phosphoregulatory acidic region in context
    • Full autoinhibited conformation not solved
  18. 2006 High

    Knock-in analysis established acidic-region Tyr174 (and Tyr142/Tyr160) as direct SH2-binding sites for Lck, PI3K p85, and PLCγ that sustain TCR microclusters and tune VAV1 phosphorylation, defining the phosphoregulatory switch.

    Evidence Vav1 Y174F knock-in mice, microcluster imaging, SH2-binding assays, development and phosphorylation analyses

    PMID:17050525

    Open questions at the time
    • Order of de-repression versus partner recruitment not resolved
    • Quantitative coupling of each tyrosine to effector arms unmeasured
  19. 2012 High

    Live-imaging and biophysical studies pinpointed that VAV1 enters SLP-76 microclusters via SH2/SH3(B) binding to SLP-76 pTyr112/128 and contributes both catalytically and as a GEF-independent scaffold, unifying its synapse recruitment mechanism.

    Evidence TIRF imaging in primary T cells, direct phosphopeptide binding measurements, domain mutants, and Ca2+ flux assays

    PMID:21386095 PMID:22956543

    Open questions at the time
    • Relative weighting of scaffolding versus GEF outputs context-dependent and unresolved
    • Stoichiometry within microclusters not defined
  20. 2016 Medium

    Identified upstream regulators (Themis1 via Grb2 stability) and non-hematopoietic roles (a Vav1-Creb-Sirt1 axis governing MSC fate), broadening the regulatory network.

    Evidence Themis1 interactome proteomics with knockout/overexpression Vav1 activity assays; Vav1-/- MSC differentiation with Sirt1/PPARγ/Sox9 acetylation assays

    PMID:26990002 PMID:27188442

    Open questions at the time
    • MSC axis single lab and mechanistically indirect
    • Generality of non-hematopoietic VAV1 function unclear
  21. 2017 High

    Established VAV1 as an oncogenic driver: ectopic expression in pancreatic carcinoma and recurrent T-cell-lymphoma mutations, deletions, and fusions augment Tyr174 phosphorylation and both catalytic and scaffolding effector pathways.

    Evidence RNAi/GEF-dead/in vivo tumor assays in pancreatic cells; binding screens, Co-IP, phospho-Tyr174 blots, and MAPK/JNK/NFAT reporter assays for lymphoma variants and RHOA G17V

    PMID:15652748 PMID:28062691 PMID:28832024

    Open questions at the time
    • Whether all variants act through a common conformational mechanism unresolved
    • No direct VAV1-targeted therapeutic validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How phosphorylation of the acidic region is structurally coupled to relief of CRD-stabilized autoinhibition in full-length VAV1, and how catalytic versus scaffolding outputs are quantitatively partitioned across different receptors, remain unresolved.
  • No full-length autoinhibited structure with the acidic region
  • Effector-arm partitioning not quantified per receptor context

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-109582 Hemostasis 1
Partners
CBLDAP10FYNGRB2ITKLCKPIK3R1SLP76
Complex memberships
DAP10-Grb2-Vav1 complexLAB-Grb2-Vav-dynamin complexSLP-76 microcluster

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 p95vav (VAV1) contains an SH2 domain and is a substrate for tyrosine protein kinases; its SH2 domain mediates association with activated EGF and PDGF receptors after ligand stimulation. In T cells, co-activation of TCR and CD4 induces rapid, transient tyrosine phosphorylation of endogenous p95vav. Deletion of the helix-loop-helix-like motif causes oncogenic activation of p95vav. Co-immunoprecipitation, domain deletion mutagenesis, tyrosine phosphorylation assays in NIH3T3 and T cells Nature High 1311423
1993 Vav immunoprecipitates from human T cell lysates possess guanine nucleotide releasing factor (GRF) activity for Ras-related GTPases; this activity increases after TCR-CD3 triggering in parallel with Vav tyrosine phosphorylation, both of which are blocked by a PTK inhibitor. Vav is also a substrate for the p56lck PTK in vitro. GRF activity assay on Vav immunoprecipitates, in vitro kinase assay with p56lck, PTK inhibitor studies Science High 8484124
1994 Vav-transformed NIH 3T3 cells maintain well-developed actin stress fibers and focal adhesions (unlike Ras-transformed cells) and do not elevate Ras-GTP levels, indicating Vav transformation is not mediated via Ras activation. Both Vav- and Dbl-transformed cells exhibit constitutively activated MAPKs (primarily ERK2), and kinase-deficient ERK1/2 inhibits Dbl transformation, implicating MAPK activation in Vav-family oncogenicity. Transformation assays in NIH 3T3 cells, Ras-GTP measurement, MAPK activity assays, dominant-negative kinase expression Molecular and Cellular Biology Medium 7935402
1995 Vav-deficient B and T cells generated by RAG-complementation show severely reduced antigen receptor-mediated proliferative responses in vitro, establishing Vav as required for BCR/TCR-induced proliferation. RAG-complementation blastocyst injection, vav null ES cells, in vitro proliferation assays Nature High 7700358
1995 Vav-deficient CD4+CD8+ thymocytes show severely impaired antigen receptor signaling and defective positive selection into mature T cells, but CD4/CD8 lineage commitment is unaffected, placing Vav in TCR-dependent maturation pathways. RAG-2 blastocyst complementation, flow cytometric analysis of thymic development, functional signaling assays Nature High 7700360
1996 Microinjection of Vav into Swiss 3T3 fibroblasts induces actin polymerization and assembly of clustered integrin complexes, and activates Rho, Rac, and Cdc42 GTPases as well as the SAPK/JNK1 MAP kinase cascade, establishing Vav as an upstream GEF regulator of Rho-family GTPases. Microinjection into Swiss 3T3 fibroblasts, actin staining, GTPase activation assays, SAPK/JNK1 kinase assays Current Biology High 8994827
1996 The Vav SH2 domain is required for its interaction with SLP-76 and for TCR-mediated tyrosine phosphorylation of Vav. Vav and SLP-76 synergistically induce NF-AT and IL-2 gene activation upon TCR stimulation, forming a signaling complex. Co-immunoprecipitation, SH2 domain mutants, reporter gene assays (NF-AT, IL-2) in Jurkat T cells, overexpression Immunity High 8673706
1997 Tyrosine phosphorylation of Vav after BCR crosslinking is positively regulated by CD19 and negatively regulated by CD22, providing a molecular mechanism for adjusting BCR signaling thresholds. BCR crosslinking in CD19-/- and CD22-/- B cells, immunoprecipitation and anti-phosphotyrosine blotting PNAS Medium 9371816
1997 Vav associates constitutively with the PI3K regulatory subunit p85 in erythropoietin-responsive cells; Vav is tyrosine phosphorylated after EPO stimulation via JAK2 (shown by in vitro kinase assay), and both Vav and PI3K are required for EPO-induced cell proliferation. Co-immunoprecipitation, in vitro PI3K activity assay, antisense vav/p85, in vitro JAK2 kinase assay Journal of Biological Chemistry Medium 9162069
1997 Cbl-b interacts with Vav through Vav's SH3-SH2-SH3 C-terminal domain and Cbl-b's proline-rich sequences; growth factor stimulation increases this affinity, leading to a trimeric complex with activated RTKs. Overexpression of Cbl-b inhibits Vav-mediated JNK activation; this inhibition requires the intact Cbl-b that binds Vav. Yeast two-hybrid, Co-immunoprecipitation, domain deletion mutants, JNK activity assay Oncogene Medium 9399639
1998 Vav-deficient T cells show defective TCR-mediated Ca2+ flux, actin polymerization, TCR clustering into patches and caps, NF-ATc1 activation, IL-2 production, and cell cycle progression (p27Kip1 downregulation). Vav constitutively associates with cytoskeletal membrane anchors talin and vinculin. In the absence of Vav, SLP-76 phosphorylation and SLP-76-talin interactions are impaired. TCR-mediated MAPK and SAPK/JNK activation was unaffected. Vav-/- mouse generation, Ca2+ flux measurements, actin polymerization assays, co-immunoprecipitation (talin, vinculin, SLP-76), cell cycle analysis Current Biology High 9601639
1998 Vav and Rac1 in NK cells regulate cell-mediated killing: Vav tyrosine phosphorylation increases during ADCC and natural killing; overexpression of Vav (but not an exchange-factor-inactive mutant) enhances killing; dominant-negative Rac1 reduces conjugate formation and impairs granule polarization toward target cells. NK cell cytotoxicity assays, overexpression of wild-type and mutant Vav, dominant-negative Rac1, granule polarization imaging Journal of Experimental Medicine Medium 9687532
1999 HIV-1 Nef binds directly to Vav (identified as the specific Nef binding partner) and activates Vav's GEF activity, leading to cytoskeletal changes (actin rearrangement) and JNK activation. Dominant-negative Vav inhibits Nef-associated kinase (NAK) activation and viral replication. Co-immunoprecipitation, GEF activity assay, dominant-negative Vav expression, cytoskeletal staining, JNK assay, viral replication assay Molecular Cell Medium 10394361
1999 hSiah2 interacts with Vav in vitro and in vivo (co-localizing in cytoplasm), requiring Vav's SH3 domain and C-terminal region of hSiah2. Overexpression of hSiah2 negatively regulates Vav-induced NFAT-dependent transcription and onco-Vav-induced JNK activation. Yeast two-hybrid, co-immunoprecipitation, co-localization by microscopy, reporter gene assays (NFAT, JNK) Molecular and Cellular Biology Medium 10207103
2000 PKCtheta function is selectively required in a Vav-dependent signaling pathway mediating TCR/CD28-induced JNK activation, IL-2 gene activation, and CD69 upregulation. Vav promotes PKCtheta translocation from cytosol to the T cell membrane/cytoskeleton and activates PKCtheta enzymatically via a pathway dependent on Rac and actin cytoskeleton reorganization. PKCtheta translocation imaging, PKCtheta kinase activity assays, dominant-negative Rac, actin disruption, reporter gene assays in T cells Immunity Medium 10714681
2000 TCR antagonists selectively activate Fyn kinase (but not Lck or ZAP-70), which phosphorylates Vav, and this Fyn-Vav-Rac1 pathway mediates cytoskeletal reorganization required for APC-T cell conjugate formation and immunological synapse. In Fyn-deficient T cells, Vav phosphorylation is deficient. Fyn-/- TCR transgenic mice, Lck/Fyn variant Jurkat cells, kinase activity assays, T cell-APC conjugate formation assay PNAS Medium 11005864
2000 Vav-1 overexpression in combination with CD28 ligation strongly activates NF-AT and permits CD28 alone to activate NF-AT without TCR engagement. This effect requires the intracellular tail of CD28, intact TCR-proximal signaling, the Vav-1 SH2 domain, and SLP-76 phosphorylation (which Vav-1 itself promotes). Vav-1 overexpression also induces lamellipodia/microspikes independent of its SH2 domain. Overexpression in Jurkat cells, NF-AT reporter assay, anti-phosphotyrosine blotting, dominant-negative/deletion mutants, microscopy Journal of Immunology Medium 11034388
2001 Vav1 is required for FcεRI-mediated activation of PLCγ1 and PLCγ2 and calcium mobilization in mast cells; it is not required for FcεRI, Syk, or LAT tyrosine phosphorylation. Reconstitution of Vav1-deficient mast cells with Vav1 restores PLCγ phosphorylation and calcium responses, demonstrating a direct role for Vav1 upstream of PLCγ. Vav1-/- mice, bone marrow-derived mast cell reconstitution, PLCγ phosphorylation assay, Ca2+ mobilization assay Molecular and Cellular Biology High 11340169
2001 Vav1 is required for TCR-induced activation of Rac1 GTPase and forms a signaling complex with Ly-GDI (hematopoietic GDI). Ly-GDI is tyrosine phosphorylated after TCR stimulation and interacts with Shc via its SH2 domain; Ly-GDI-Vav1 interaction requires tyrosine phosphorylation. Co-expression of Ly-GDI enhances Vav1-induced NFAT activation and PLCγ phosphorylation; this cooperativity requires their physical association. Co-immunoprecipitation, reporter gene assays (NFAT), PLCγ phosphorylation, Ca2+ mobilization, oncogenic Vav1 (non-binding) as control Journal of Biological Chemistry Medium 12386169
2002 Vav1 is required for TCR-induced integrin clustering and MHC/peptide-specific T cell adhesion to APCs. Vav1-deficient thymocytes and T cells show impaired integrin-mediated adhesion to ECM proteins and ICAM-1. Integrin and TCR clustering are controlled by distinct pathways: integrin clustering is Vav1-dependent and WASP-independent. Vav1-/- mice, adhesion and aggregation assays, peptide-loaded APC systems, comparison with WASP-/- cells Immunity High 11911819
2002 Vav1 has a nuclear localization that occurs in a receptor stimulation-dependent manner, requiring the C-terminal SH3 domain and a nuclear localization sequence within the PH domain. Nuclear Vav1 is an integral component of NFAT- and NFκB-like transcriptionally active complexes, with the C-terminal SH3 domain critical for their formation. Subcellular fractionation, nuclear localization by imaging, chromatin co-immunoprecipitation with NFAT/NFκB complexes, domain deletion mutants Journal of Experimental Medicine Medium 11994417
2003 Cbl ubiquitin ligase mediates Vav ubiquitinylation in a manner requiring Cbl/Vav association through phosphorylated Tyr-700 on Cbl and an intact Cbl RING finger domain; this promotes loss of phosphorylated Vav. Cbl (but not its ubiquitin ligase mutant) inhibits Vav-dependent signaling. Immortalized T cells from Cbl+/+ and Cbl-/- mice, 293T transfection, ubiquitin assays, RING finger mutant controls Journal of Biological Chemistry Medium 12881521
2003 Vav1 is required for TCR-induced activation of the LFA-1 integrin (inside-out signaling), which explains the defect in conjugate formation with APCs. However, once conjugates form in the absence of Vav1, immunological synapse assembly is normal. Vav1 is required for MTOC polarization but not for synapse protein organization. Vav1-/- double-positive thymocytes, conjugate formation assays with peptide-loaded APCs, LFA-1 activation assay, MTOC polarization imaging European Journal of Immunology Medium 12616499
2003 Vav1/2/3-null mice produce no functional T or B cells and fail to mount humoral responses. The Vav family is essential for both TCR- and BCR-induced Ca2+ signaling. Vav family is required for MAPK activation in T cells but not in B cells, revealing lineage-specific roles. Vav1 alone is sufficient for normal lymphocyte development; Vav3 plays a compensatory role in T cells. Triple vav1/2/3 knockout mice, flow cytometry, Ca2+ flux assays, MAPK activation assays, reconstitution experiments Journal of Experimental Medicine High 14623913
2003 Vav1 transduces TCR signals to ERK activation via a pathway involving Ras GTPase and B-Raf, MEK1/2 kinases. Vav1 controls membrane recruitment of two Ras GEFs: RasGRP1 (via PLCγ1) and Sos1/2 (via LAT). Vav1 is required for TCR-induced LAT phosphorylation, which is the key upstream event for both PLCγ1 and Sos1/2 activation. Vav1-/- double-positive thymocytes, ERK/Ras activation assays, RasGRP1/Sos membrane recruitment assays, LAT phosphorylation assays Journal of Biological Chemistry High 14764585
2003 Vav-1 constitutively associates with IKKα (but not IKKβ) through their helix-loop-helix domains; CD28 engagement increases Vav-1-associated IKKα kinase activity. Vav-1 and IKKα colocalize at the membrane after CD28 stimulation, and Vav-1 promotes NF-κB activation via IKKα. Co-immunoprecipitation in Jurkat and primary CD4+ T cells, IKKα kinase assay, domain interaction mapping, confocal microscopy, reporter assays Journal of Immunology Medium 12626540
2004 Vav1 and Vav3 have critical but redundant roles in mediating platelet activation by GPVI collagen receptor: Vav1/Vav3 double-deficient platelets show marked inhibition of aggregation and spreading with reduced PLCγ2 tyrosine phosphorylation. Triple Vav1/2/3-deficient platelets show a similar phenotype to Vav1/3-deficient cells. Vav1-/-, Vav3-/-, Vav1/3-/-, Vav1/2/3-/- mice, platelet aggregation assay, spreading assay, PLCγ2 phosphorylation Journal of Biological Chemistry High 15456756
2005 Vav1 is ectopically expressed in pancreatic adenocarcinomas due to promoter demethylation. In pancreatic cancer cells, Vav1 acts synergistically with EGFR to stimulate cell proliferation via GEF activity toward Rac1, leading to PAK1 and NF-κB activation and cyclin D1 upregulation. Vav1 RNAi abrogates neoplastic proliferation in vitro and in vivo even in the presence of oncogenic KRAS. RNAi knockdown, GEF-inactive mutants, in vitro and in vivo tumor growth assays, NF-κB reporter, Rac1 activation assay, bisulfite sequencing Cancer Cell High 15652748
2005 CXCL12 (chemokine) promotes T lymphocyte α4β1 integrin-dependent adhesion via activation of Vav1 and its downstream effector Rac; siRNA knockdown of Vav1 blocks Rac activation by CXCL12, impairs integrin-dependent adhesion strengthening, and inhibits transendothelial migration. siRNA knockdown of Vav1, dominant-negative Vav1/Rac, Rac activation assay, flow chamber adhesion assays, transendothelial migration assay Molecular Biology of the Cell Medium 15872091
2005 Itk is constitutively associated with Vav1; kinase-inactive Itk rescues TCR-induced Vav localization and actin polarization defects caused by Itk siRNA knockdown, demonstrating a kinase-independent scaffolding function of Itk for Vav recruitment to the site of antigen contact. Loss of Itk disrupts Vav-SLP-76 interactions. siRNA knockdown, kinase-dead/PH/SH2-mutant Itk re-expression, Vav localization imaging, co-immunoprecipitation, membrane-targeted Vav-CAAX rescue Journal of Immunology Medium 15661896
2005 Vav1 deficiency impairs TCR/CD28-induced Akt phosphorylation and FOXO1 phosphorylation, reducing FOXO1 cytoplasmic localization and its association with 14-3-3τ, resulting in failure to downregulate p27kip1 and causing G0-G1 cell cycle arrest. This places Vav1 in a PI3K/Akt/FOXO1/p27kip1 pathway controlling T cell cycle progression. Vav1-/- T cells, Akt/FOXO1 phosphorylation assays, 14-3-3τ Co-IP, cell cycle analysis by FACS, p27kip1 expression Journal of Immunology Medium 17015685
2006 Vav1 is required for DAP10-mediated NK cell cytotoxicity but is not required for ITAM (DAP12/FcRγ)-mediated cytotoxicity; Vav1 interacts with DAP10 YxNM motifs through the adaptor Grb2, and is required for PI3K-dependent Akt signaling and cytoskeletal polarization (actin and microtubule) at the cytolytic synapse. Vav1-/- and Vav1/DAP12-double-deficient mice, cytotoxicity assays, cytoskeletal polarization imaging, Co-IP of Vav1-Grb2-DAP10, Akt activation assay Journal of Immunology High 16582911 16887996
2006 NKG2D-DAP10-mediated cytotoxicity in human NK cells requires a DAP10-bound Grb2-Vav1 intermediate; Grb2-Vav1 binding to DAP10 is sufficient to initiate tyrosine phosphorylation events. Full calcium release and cytotoxicity requires both Grb2-Vav1 and PI3K p85 to bind DAP10. Co-immunoprecipitation of DAP10-Grb2-Vav1 complex, cytotoxicity assays, calcium flux assays with DAP10 mutants Nature Immunology High 16582911
2006 Vav1 and Vav3 are specifically required for integrin (complement receptor αMβ2)-mediated phagocytosis in macrophages, controlling Arp2/3 recruitment and actin polymerization at the complement-induced phagosome. Constitutively active Rac rescues actin polymerization and phagocytosis in Vav-deficient macrophages, placing Vav upstream of Rac in this pathway. Vav1/3 is not required for FcγR-mediated phagocytosis. Vav1-/-, Vav3-/-, Rac1/2-/- primary murine macrophages, phagocytosis assays, Arp2/3 and actin imaging, constitutively active Rac rescue Immunity High 16546099
2006 Vav1 acidic-region tyrosine Tyr174 is required for the maintenance of TCR-signaling microclusters and normal T cell development and activation. The acidic-region tyrosines (Tyr142, Tyr160, Tyr174) conform to SH2-binding motifs and directly bind SH2 domains of Lck, PI3K p85α, and PLCγ1. These tyrosines also regulate Vav1 tyrosine phosphorylation levels. Constitutively activated Vav1 GEF disrupts TCR-signaling microclusters. Knock-in mice (Vav1 Y174F), microcluster imaging by TIRF/confocal microscopy, SH2 domain binding assays, T cell development assays, Vav1 phosphorylation analysis Journal of Biological Chemistry High 17050525
2008 Crystal structure of Vav1 DH-PH-CRD in complex with Rac1 at 2.6 Å resolution reveals a unique intramolecular network of contacts between the Vav1 cysteine-rich domain (CRD) and the C-terminal helix of the DH domain that stabilizes the DH domain for intimate association with the Switch II region of Rac1, displacing the guanine nucleotide. Mutational analysis confirms the CRD is critical for optimal GEF activity and GTPase specificity breadth. X-ray crystallography (2.6 Å), SAXS, site-directed mutagenesis + GEF activity assay Journal of Molecular Biology High 18589439
2009 Vav1 and Vav3 (but not Vav2) are required for BCR endocytosis and BCR-induced Rac-GTP loading, but not for BCR signaling to MHC-II/CD80 expression or for B cell development/maturation. Vav1-/-, Vav3-/- B cells, BCR endocytosis assay, Rac activation assay, antigen presentation assay Journal of Biological Chemistry Medium 19586920
2009 BCR endocytosis is supported by a sequential pathway: tyrosine phosphorylation of adaptor LAB recruits a Grb2-dynamin complex and Vav; Vav activates Rac1 and Rac2, all of which are required for BCR endocytosis and antigen presentation. LAB phosphorylation assays, co-immunoprecipitation of LAB-Grb2-Vav complex, Rac activation, BCR endocytosis assay Journal of Biological Chemistry Medium 19858206
2009 Vav1 is required for Dectin-1-mediated phagocytosis of β-glucan and subsequent superoxide production in microglia; Vav1 functions upstream of PI3K and is required for PI3K activation in this pathway. Vav1 siRNA knockdown, PI3K activation assay, phagocytosis assay, superoxide production assay, ordering by inhibitor analysis Molecular Immunology Medium 19232731
2011 Vav1 enters SLP-76 microclusters via its C-terminal SH2 and SH3(B) domains, which bind directly to phosphotyrosines 112 and 128 of SLP-76. Both the C-terminal (SH) and N-terminal (GEF) regions of Vav1 contribute to stabilization of SLP-76 microclusters in a GEF-activity-independent manner. The CH domain and catalytic core of the GEF differentially affect Ca2+ responses. Live TIRF imaging of microclusters, biophysical Vav1-SLP76 binding measurements, deletion and point mutants, Ca2+ flux assays Science Signaling High 21386095
2012 Vav1 is recruited to immunological synapse microclusters in primary T cells; this recruitment depends on the SH2 and C-terminal SH3 (SH3B) domains of Vav1 and on phosphotyrosines 112 and 128 of SLP-76. These same domains are critical for Vav1 tyrosine phosphorylation and TCR-induced Ca2+ flux. Live imaging of primary CD4+ and CD8+ T cells, biophysical direct binding assay (Vav1 to SLP76 phosphopeptides), domain deletion/point mutants, Ca2+ flux assays Journal of Cell Science High 22956543
2013 Vav1 is a central regulator of invadopodia assembly in pancreatic tumor cells; its GEF activity toward Cdc42 is required for invadopodia formation. Src-mediated phosphorylation (at Tyr174) activates Vav1 and is sufficient for invadopodia formation; the phosphomimetic Vav1-Y174F drives invadopodia even without Src activation. siRNA knockdown of Vav1, GEF-inactive and Y174F mutants, invadopodia assay (gelatin degradation), Cdc42 activation, Src inhibitor treatment Current Biology Medium 24332539
2013 BTK and Vav1 are recruited to Dectin-1-associated phagocytic cups containing Candida albicans; they colocalize with PI(3,4,5)P3 and F-actin. BTK and Vav1-deficient macrophages show defective phagocytosis of C. albicans, and Vav1-/- mice are more susceptible to systemic C. albicans infection. Co-immunoprecipitation with Dectin-1, confocal localization in phagocytic cups, Vav1-/- macrophages and mice, phagocytosis assay, infection susceptibility PLoS Pathogens Medium 23825946
2016 Themis1 promotes Vav1 activity in developing thymocytes both in vitro and in vivo by maintaining Grb2 stability; loss of Themis1 reduces Grb2 levels leading to reduced Vav1 activity and impaired T cell development. Proteomic analysis identifies SHP-1, Grb2, and Vav1 as principal Themis1 interacting partners in thymocytes. Quantitative proteomics of Themis1 interactome, TCR reporter mice, Vav1 activity assays in Themis1-/- and overexpressing thymocytes, Grb2 degradation assay Science Signaling Medium 27188442
2016 Loss of Vav1 in mesenchymal stem cells (MSCs) reduces Sirt1 levels via Creb, leading to increased acetylation of PPARγ (promoting adipogenesis) and Sox9 (repressing chondrogenesis). Thus Vav1 controls MSC fate decisions between adipocyte and chondrocyte differentiation through a Vav1-Creb-Sirt1 axis. Vav1-/- mice, ectopic Vav1 expression rescue, Sirt1/PPARγ/Sox9 acetylation and expression assays, Creb phosphorylation, adipogenesis and chondrogenesis assays Stem Cells Medium 26990002
2017 The G17V RHOA mutant (found in AITL) specifically binds VAV1 and augments its adaptor function through increased phosphorylation of Tyr174, accelerating TCR signaling. VAV1 mutations and a VAV1-STAP2 translocation fusion found in PTCL also augment Tyr174 phosphorylation and TCR signaling. High-throughput protein binding screen, Co-immunoprecipitation, phospho-VAV1 (Tyr174) Western blot, TCR signaling assays, clinical specimen staining Leukemia Medium 28832024
2017 In peripheral T cell lymphomas, a recurrent in-frame VAV1 deletion (Δ778-786) and VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, VAV1-S100A7) result in increased activation of both catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (NFAT) VAV1 effector pathways, supporting a driver oncogenic role. RNA sequencing, targeted sequencing, MAPK/JNK/NFAT reporter assays in cells expressing the VAV1 variants PNAS Medium 28062691
2005 The CRD domain of Vav1/Vav2 plays an active role in both the initial binding event (kon) with Rac1 and the rate-limiting dissociation step (kcat) during guanine nucleotide exchange; Vav2-mediated exchange follows a Theorell-Chance mechanism. NMR chemical shift mapping shows the isolated Vav1 CRD directly associates with Rac1 near the P-loop and guanine base. In vitro GEF kinetic assays, fluorescence anisotropy, NMR chemical shift mapping, site-directed mutagenesis of Rac1 and CRD Biochemistry High 15850391

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav. Nature 372 7700358
1998 Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor. Current biology : CB 348 9601639
1992 Product of vav proto-oncogene defines a new class of tyrosine protein kinase substrates. Nature 302 1311423
1993 Tyrosine kinase-stimulated guanine nucleotide exchange activity of Vav in T cell activation. Science (New York, N.Y.) 297 8484124
1996 Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation. Immunity 286 8673706
1995 Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes. Nature 282 7700360
2005 Vav-family proteins in T-cell signalling. Current opinion in immunology 272 15886116
2002 VAV proteins as signal integrators for multi-subunit immune-recognition receptors. Nature reviews. Immunology 267 12094222
1999 Biological and regulatory properties of Vav-3, a new member of the Vav family of oncoproteins. Molecular and cellular biology 237 10523675
1998 Phosphorylation-dependent and constitutive activation of Rho proteins by wild-type and oncogenic Vav-2. The EMBO journal 230 9822605
2006 NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells. Nature immunology 219 16582911
1999 Activation of Vav by Nef induces cytoskeletal rearrangements and downstream effector functions. Molecular cell 205 10394361
2003 Vav1/2/3-null mice define an essential role for Vav family proteins in lymphocyte development and activation but a differential requirement in MAPK signaling in T and B cells. The Journal of experimental medicine 186 14623913
2004 Vav proteins, masters of the world of cytoskeleton organization. Cellular signalling 185 14607270
1996 Faciogenital dysplasia protein (FGD1) and Vav, two related proteins required for normal embryonic development, are upstream regulators of Rho GTPases. Current biology : CB 182 8994827
2000 A novel functional interaction between Vav and PKCtheta is required for TCR-induced T cell activation. Immunity 181 10714681
2005 Ectopic expression of VAV1 reveals an unexpected role in pancreatic cancer tumorigenesis. Cancer cell 177 15652748
2001 Vav proteins, adaptors and cell signaling. Oncogene 172 11607839
2006 Requirements for Vav guanine nucleotide exchange factors and Rho GTPases in FcgammaR- and complement-mediated phagocytosis. Immunity 152 16546099
2002 Vav1 controls integrin clustering and MHC/peptide-specific cell adhesion to antigen-presenting cells. Immunity 149 11911819
1998 The Vav-Rac1 pathway in cytotoxic lymphocytes regulates the generation of cell-mediated killing. The Journal of experimental medicine 147 9687532
1994 Dbl and Vav mediate transformation via mitogen-activated protein kinase pathways that are distinct from those activated by oncogenic Ras. Molecular and cellular biology 139 7935402
2001 Compensation between Vav-1 and Vav-2 in B cell development and antigen receptor signaling. Nature immunology 136 11376343
2014 Vav family exchange factors: an integrated regulatory and functional view. Small GTPases 128 25483299
2000 Vav family proteins couple to diverse cell surface receptors. Molecular and cellular biology 128 10938113
2001 Vav1 regulates phospholipase cgamma activation and calcium responses in mast cells. Molecular and cellular biology 120 11340169
2005 Kinase-independent functions for Itk in TCR-induced regulation of Vav and the actin cytoskeleton. Journal of immunology (Baltimore, Md. : 1950) 108 15661896
2017 Activation of RHOA-VAV1 signaling in angioimmunoblastic T-cell lymphoma. Leukemia 105 28832024
2017 Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas. Proceedings of the National Academy of Sciences of the United States of America 100 28062691
2004 Differential requirements for Vav proteins in DAP10- and ITAM-mediated NK cell cytotoxicity. The Journal of experimental medicine 93 15365099
2003 Vav1: a key signal transducer downstream of the TCR. Immunological reviews 91 12670394
1993 Developmental expression of the vav protooncogene. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 88 8494792
1997 CD19 and CD22 expression reciprocally regulates tyrosine phosphorylation of Vav protein during B lymphocyte signaling. Proceedings of the National Academy of Sciences of the United States of America 87 9371816
1998 Transcriptional regulation of vav, a gene expressed throughout the hematopoietic compartment. Blood 81 9427694
2004 Vav1 transduces T cell receptor signals to the activation of the Ras/ERK pathway via LAT, Sos, and RasGRP1. The Journal of biological chemistry 80 14764585
2004 Vav1 and vav3 have critical but redundant roles in mediating platelet activation by collagen. The Journal of biological chemistry 80 15456756
2003 Vav1 transduces TCR signals required for LFA-1 function and cell polarization at the immunological synapse. European journal of immunology 80 12616499
2005 Vav1 and Rac control chemokine-promoted T lymphocyte adhesion mediated by the integrin alpha4beta1. Molecular biology of the cell 77 15872091
2006 Vav1 controls DAP10-mediated natural cytotoxicity by regulating actin and microtubule dynamics. Journal of immunology (Baltimore, Md. : 1950) 76 16887996
2013 Bruton's Tyrosine Kinase (BTK) and Vav1 contribute to Dectin1-dependent phagocytosis of Candida albicans in macrophages. PLoS pathogens 75 23825946
1997 Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation. Oncogene 75 9399639
2014 P-Rex and Vav Rac-GEFs in platelets control leukocyte recruitment to sites of inflammation. Blood 74 25538043
1998 Vav links antigen-receptor signaling to the actin cytoskeleton. Seminars in immunology 72 9695188
2010 P-Rex1 and Vav1 cooperate in the regulation of formyl-methionyl-leucyl-phenylalanine-dependent neutrophil responses. Journal of immunology (Baltimore, Md. : 1950) 70 21178006
2000 CD28 utilizes Vav-1 to enhance TCR-proximal signaling and NF-AT activation. Journal of immunology (Baltimore, Md. : 1950) 70 11034388
2001 Functional dichotomy in natural killer cell signaling: Vav1-dependent and -independent mechanisms. The Journal of experimental medicine 69 11413196
2002 Vav1 is a component of transcriptionally active complexes. The Journal of experimental medicine 67 11994417
2002 Vav1 and Ly-GDI two regulators of Rho GTPases, function cooperatively as signal transducers in T cell antigen receptor-induced pathways. The Journal of biological chemistry 60 12386169
1996 The VAV family of signal transduction molecules. Critical reviews in oncogenesis 60 9109498
2019 The Vav GEF Family: An Evolutionary and Functional Perspective. Cells 53 31100928
2015 hCD2-iCre and Vav-iCre mediated gene recombination patterns in murine hematopoietic cells. PloS one 53 25884630
2009 B cell antigen receptor endocytosis and antigen presentation to T cells require Vav and dynamin. The Journal of biological chemistry 52 19586920
2003 Cbl-mediated ubiquitinylation and negative regulation of Vav. The Journal of biological chemistry 52 12881521
2013 Vav1 as a central regulator of invadopodia assembly. Current biology : CB 50 24332539
2006 Vav1 promotes T cell cycle progression by linking TCR/CD28 costimulation to FOXO1 and p27kip1 expression. Journal of immunology (Baltimore, Md. : 1950) 50 17015685
2008 Structural basis of guanine nucleotide exchange mediated by the T-cell essential Vav1. Journal of molecular biology 48 18589439
1997 Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity. The Journal of biological chemistry 48 9162069
2018 Protective effects of microRNA-330 on amyloid β-protein production, oxidative stress, and mitochondrial dysfunction in Alzheimer's disease by targeting VAV1 via the MAPK signaling pathway. Journal of cellular biochemistry 47 29369410
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
2001 Vav-1 regulates NK T cell development and NK cell cytotoxicity. European journal of immunology 47 11500824
2000 T-cell receptor antagonists induce Vav phosphorylation by selective activation of Fyn kinase. Proceedings of the National Academy of Sciences of the United States of America 47 11005864
2002 Regulation of Vav proteins by intramolecular events. Frontiers in bioscience : a journal and virtual library 46 11779690
1996 Structure and function of vav. Cellular signalling 45 9115846
2013 GTP exchange factor Vav regulates guided cell migration by coupling guidance receptor signalling to local Rac activation. Journal of cell science 44 23525006
2003 Vav-1 and the IKK alpha subunit of I kappa B kinase functionally associate to induce NF-kappa B activation in response to CD28 engagement. Journal of immunology (Baltimore, Md. : 1950) 43 12626540
2000 Specific subdomains of Vav differentially affect T cell and NK cell activation. Journal of immunology (Baltimore, Md. : 1950) 43 10754287
1997 Thrombopoietin and thrombin induce tyrosine phosphorylation of Vav in human blood platelets. Blood 43 9108397
2005 Impaired IL-4 and c-Maf expression and enhanced Th1-cell development in Vav1-deficient mice. Blood 41 15845902
2005 The Vav family: at the crossroads of signaling pathways. Immunologic research 41 16106078
2005 Recognition and activation of Rho GTPases by Vav1 and Vav2 guanine nucleotide exchange factors. Biochemistry 40 15850391
2009 Vav1 and PI3K are required for phagocytosis of beta-glucan and subsequent superoxide generation by microglia. Molecular immunology 39 19232731
2005 Vav proteins regulate peripheral B-cell survival. Blood 39 15941910
2003 Guanine exchange-dependent and -independent effects of Vav1 on integrin-induced T cell spreading. Journal of immunology (Baltimore, Md. : 1950) 39 12496381
1999 hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways. Molecular and cellular biology 39 10207103
2008 Vav1: a hematopoietic signal transduction molecule involved in human malignancies. The international journal of biochemistry & cell biology 38 19100858
2007 Flesh and blood: the story of Vav1, a gene that signals in hematopoietic cells but can be transforming in human malignancies. Cancer letters 38 17590270
2005 Vav proteins are required for B-lymphocyte responses to LPS. Blood 38 15811961
2009 Vav GEFs regulate macrophage morphology and adhesion-induced Rac and Rho activation. Experimental cell research 37 19715691
2004 Role of vav1- and src-related tyrosine kinases in macrophage activation by CpG DNA. The Journal of biological chemistry 37 14749335
2003 Vav1: an oncogene that regulates specific transcriptional activation of T cells. Blood 37 14592821
2016 Themis1 enhances T cell receptor signaling during thymocyte development by promoting Vav1 activity and Grb2 stability. Science signaling 35 27188442
2009 Vav1 regulates the migration and adhesion of dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 34 19542442
2006 Vav1 acidic region tyrosine 174 is required for the formation of T cell receptor-induced microclusters and is essential in T cell development and activation. The Journal of biological chemistry 34 17050525
2005 Vav1 and Vav2 play different roles in macrophage migration and cytoskeletal organization. Experimental cell research 34 16137676
2003 Independent CD28 signaling via VAV and SLP-76: a model for in trans costimulation. Immunological reviews 34 12670393
2016 Vav1 Regulates Mesenchymal Stem Cell Differentiation Decision Between Adipocyte and Chondrocyte via Sirt1. Stem cells (Dayton, Ohio) 32 26990002
2009 IDO inhibits T-cell function through suppressing Vav1 expression and activation. Cancer biology & therapy 32 19597340
2009 Vav and Rac activation in B cell antigen receptor endocytosis involves Vav recruitment to the adapter protein LAB. The Journal of biological chemistry 32 19858206
2015 Vav1 Regulates T-Cell Activation through a Feedback Mechanism and Crosstalk between the T-Cell Receptor and CD28. Journal of proteome research 31 26043137
2002 Vav1 couples T cell receptor to serum response factor-dependent transcription via a MEK-dependent pathway. The Journal of biological chemistry 31 11859076
2012 Mechanism and function of Vav1 localisation in TCR signalling. Journal of cell science 29 22956543
2016 TGFβ promotes mesenchymal phenotype of pancreatic cancer cells, in part, through epigenetic activation of VAV1. Oncogene 28 27893715
2009 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. Experimental cell research 28 19747912
2011 CDC25A, VAV1, TP73, BRCA1 and ZAP70 gene overexpression correlates with radiation response in colorectal cancer. Oncology reports 27 21344162
2011 Vav1-mediated scaffolding interactions stabilize SLP-76 microclusters and contribute to antigen-dependent T cell responses. Science signaling 27 21386095
1996 Vav: function and regulation in hematopoietic cell signaling. Stem cells (Dayton, Ohio) 27 8724692
2008 The Gammaherpesvirus m2 protein manipulates the Fyn/Vav pathway through a multidocking mechanism of assembly. PloS one 26 18301737
2014 Phosphatidylinositol 4-phosphate 5-kinase α and Vav1 mutual cooperation in CD28-mediated actin remodeling and signaling functions. Journal of immunology (Baltimore, Md. : 1950) 25 25539813
2002 CD28 costimulation: a source of Vav-1 for TCR signaling with the help of SLP-76? Science's STKE : signal transduction knowledge environment 25 12165654
2001 Protein kinase C theta cooperates with Vav1 to induce JNK activity in T-cells. The Journal of biological chemistry 25 11274147

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