Affinage

VASP

Vasodilator-stimulated phosphoprotein · UniProt P50552

Length
380 aa
Mass
39.8 kDa
Annotated
2026-04-28
100 papers in source corpus 45 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VASP is an actin regulatory protein that functions as a processive barbed-end elongation factor, antagonizing capping protein and promoting filament extension through its WH2 domain-mediated delivery of G-actin monomers to growing filament ends (PMID:12086607, PMID:18923426, PMID:21217643). It is recruited to focal adhesions, the leading edge, filopodial tips, and pathogen surfaces via its EVH1 domain, which binds proline-rich motifs in vinculin, zyxin, ActA, Lamellipodin, and IRSp53; CDC42-activated IRSp53 clusters VASP on membranes to initiate filopodia, and VASP forms liquid-like condensates that drive parallel actin bundle assembly (PMID:8836115, PMID:24076653, PMID:36240267, PMID:38405682). VASP activity is regulated by multisite phosphorylation—PKA/PKCδ at Ser157 controls membrane localization and partner binding (vinculin, αII-spectrin, CRKL), PKG at Ser239 modulates anti-capping activity and NF-κB-dependent inflammatory signaling, and AMPK at Ser322 alters actin binding—with dephosphorylation governed by PP1 and PP2A (PMID:10087267, PMID:18195108, PMID:27620165, PMID:33106416, PMID:21945940, PMID:7656973). VASP is essential for cyclic nucleotide-mediated inhibition of platelet aggregation downstream of the NO/cGMP/PKG pathway, regulates endothelial barrier integrity and T-cell diapedesis, and contributes to lamellipodial protrusion, integrin-mediated adhesion, and traction force generation (PMID:9878048, PMID:12933589, PMID:28320969, PMID:32391788).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1992 High

    The identification of VASP as a novel F-actin-binding phosphoprotein that is stoichiometrically phosphorylated by both PKA and PKG in platelets established VASP as a convergence point for cyclic nucleotide signaling and the actin cytoskeleton.

    Evidence Subcellular fractionation, immunofluorescence, direct F-actin binding assay, and in vivo phosphorylation in intact human platelets

    PMID:1318192

    Open questions at the time
    • No identification of specific phosphorylation sites
    • Functional consequence of phosphorylation on actin binding not determined
    • Mechanism of VASP recruitment to focal contacts unknown
  2. 1995 High

    Discovery that VASP directly binds profilins via its proline-rich domain and that its phosphorylation state is dynamically controlled by PP1/PP2A phosphatases established VASP as a regulated profilin-actin pathway component.

    Evidence Direct binding assays with purified profilins from multiple species; okadaic acid treatment of platelets with in vitro phosphatase selectivity analysis

    PMID:7656973 PMID:7737110

    Open questions at the time
    • Whether profilin binding is required for VASP function in actin dynamics not tested
    • Relative contributions of individual phosphatases to specific VASP sites in vivo unknown
  3. 1996 High

    Mapping VASP's EVH1 domain as the targeting module for proline-rich motifs in vinculin and Listeria ActA explained how VASP is recruited to focal adhesions and pathogen surfaces, defining a general recruitment logic for Ena/VASP proteins.

    Evidence In vitro binding with domain-mapping mutagenesis, GST-pulldowns, and co-localization in fibroblasts and Listeria-infected cells

    PMID:8836115 PMID:8861907

    Open questions at the time
    • Whether EVH1-mediated recruitment is sufficient for VASP function at each site not tested
    • Full repertoire of EVH1-binding partners unknown
  4. 1999 High

    Quantitative biochemistry revealed that PKA phosphorylation at Ser157 increases VASP's F-actin affinity ~40-fold, and electrostatic mutagenesis of the EVH1 domain defined the structural basis for proline-rich motif recognition, establishing the first mechanistic links between phosphorylation, domain function, and actin binding.

    Evidence In vitro motility assay with recombinant VASP add-back, quantitative binding measurements, EVH1 charge-reversal mutagenesis with rescue

    PMID:10087267 PMID:10498433

    Open questions at the time
    • How Ser157 phosphorylation structurally alters actin binding not resolved
    • Whether phosphorylation regulates EVH1 ligand recognition not tested
  5. 1999 High

    VASP knockout mice revealed that VASP is required specifically for cAMP/cGMP-mediated inhibition of platelet aggregation but dispensable for smooth muscle relaxation, defining VASP's non-redundant physiological role in platelet cyclic nucleotide signaling.

    Evidence VASP-null mice with platelet aggregation, calcium, granule secretion, and smooth muscle tension assays

    PMID:9878048

    Open questions at the time
    • Molecular mechanism by which VASP inhibits platelet activation not identified
    • Compensation by Mena/EVL in smooth muscle not excluded
  6. 2000 High

    Dose-dependent modulation of fibroblast motility by Ena/VASP proteins, with membrane-targeted VASP inhibiting motility, established that VASP at the leading edge (not focal adhesions) is the functionally relevant pool for cell migration.

    Evidence Selective depletion and constitutive membrane targeting of Ena/VASP proteins with cell migration assays

    PMID:10892743

    Open questions at the time
    • How leading-edge VASP alters actin network architecture to slow motility not resolved
    • Relative contributions of individual Ena/VASP family members not separated
  7. 2002 High

    The demonstration that Ena/VASP proteins associate with barbed ends, shield them from capping protein, and produce longer less-branched filaments established the core anti-capping/elongation mechanism; systematic mutagenesis showed the EVH2 domain and phosphorylation sites are essential for motility while profilin binding is dispensable.

    Evidence In vitro barbed-end capping assay, EM of actin networks, complementation of Ena/VASP-null cells with domain mutants

    PMID:12086607 PMID:12134077 PMID:12134088

    Open questions at the time
    • Whether VASP is truly processive at barbed ends or transiently protective not resolved
    • Structural basis of barbed-end association unknown
  8. 2004 High

    Identification of Lamellipodin and RIAM as EVH1-binding scaffolds that recruit VASP downstream of PI3K and Rap1 signaling, respectively, placed VASP within defined upstream signaling cascades controlling lamellipodial protrusion and integrin activation.

    Evidence Co-immunoprecipitation, co-localization at lamellipodia/filopodia tips, functional epistasis with Lpd/RIAM overexpression and knockdown

    PMID:15469845 PMID:15469846

    Open questions at the time
    • Relative contributions of Lpd versus RIAM to VASP recruitment in different cell types unknown
    • Structural basis of Lpd-VASP interaction not determined
  9. 2006 High

    Zyxin was established as the principal recruiter of Ena/VASP to focal adhesions (zyxin-null cells lose focal adhesion VASP), and PKCδ was identified as a constitutive VASP-interacting kinase that negatively regulates Ser157 phosphorylation and filopodia formation, revealing two new upstream regulators.

    Evidence Zyxin knockout fibroblasts with VASP localization analysis; PKCδ/VASP double-KO platelet epistasis experiments

    PMID:16505170 PMID:16940418

    Open questions at the time
    • Whether zyxin-dependent VASP localization is functionally important for stress fiber repair not directly tested
    • PKCδ phosphorylation site on VASP not mapped
  10. 2007 High

    Multiple discoveries clarified phosphorylation-dependent partner switching: Ser157 phosphorylation by PKA inhibits αII-spectrin and CRKL binding, while Ser239 phosphorylation by PKG causes lamellipodial retraction and enables TRPC4 association, establishing site-specific phosphorylation as a mechanism for VASP functional diversification.

    Evidence Phospho-state-dependent Co-IP, VASP Ser239Ala mutagenesis with live-cell imaging, VASP-KO endothelial permeability assays, TRPC4 phospho-dependent Co-IP

    PMID:17684063 PMID:17913834 PMID:18195108

    Open questions at the time
    • Structural mechanism of phosphorylation-induced partner switching not resolved
    • Whether Ser239-TRPC4 interaction is direct not established
  11. 2008 High

    TIRF microscopy demonstrated that clustered VASP switches to processive filament elongation insensitive to capping protein, with WH2 domains delivering G-actin to barbed ends, resolving the long-standing question of whether VASP is a true processive polymerase.

    Evidence In vitro TIRF with VASP-coated beads, WH2 domain mutagenesis, quantitative elongation kinetics

    PMID:18923426

    Open questions at the time
    • Cluster size and stoichiometry required for processivity not defined
    • How tetramerization contributes to processivity not structurally resolved
  12. 2011 High

    Kinetic analysis revealed that VASP elongation rate is determined by WH2-mediated G-actin recruitment with saturation kinetics, and AMPK was identified as a kinase phosphorylating the novel site Ser322 to alter actin binding, expanding the regulatory repertoire beyond PKA/PKG.

    Evidence TIRF with chimeric VASP constructs and mathematical modeling; in vitro AMPK kinase assay with MS phosphosite mapping

    PMID:21217643 PMID:21945940

    Open questions at the time
    • Physiological context for AMPK-VASP regulation not established
    • Whether Ser322 phosphorylation affects processivity not tested
  13. 2013 High

    Reconstitution showed that CDC42-activated IRSp53 recruits and clusters VASP on membranes to initiate processive elongation and filopodium formation, identifying the minimal signaling module for filopodium initiation.

    Evidence In vitro TIRF actin polymerization, liposome recruitment assay with purified IRSp53/VASP/CDC42

    PMID:24076653

    Open questions at the time
    • Whether other membrane curvature sensors can substitute for IRSp53 unknown
    • Regulation of IRSp53-VASP clustering dynamics in vivo not defined
  14. 2015 High

    Lamellipodin was shown to bind actin filaments directly and enhance VASP polymerase activity by tethering it to filaments, while VASP Ser157 phosphorylation was found necessary for membrane localization and vinculin-dependent actin polymerization in smooth muscle, refining the delivery and activation model.

    Evidence In vitro Lpd-actin binding and TIRF polymerization assays; VASP S157A mutant expression in smooth muscle with Co-IP and tension measurement

    PMID:25759389 PMID:26295568

    Open questions at the time
    • Whether Lpd tethering model applies to all cell types not tested
    • Structural basis of Lpd enhancement of VASP processivity unknown
  15. 2017 High

    EVL/VASP double-knockout T cells showed a specific defect in diapedesis but not adhesion or crawling, mediated through altered α4 integrin regulation, establishing a non-redundant role for Ena/VASP in immune cell transendothelial migration.

    Evidence EVL/VASP double-KO mice, intravital microscopy, transendothelial migration under shear, α4 integrin blockade rescue

    PMID:28320969

    Open questions at the time
    • Mechanism by which VASP regulates α4 integrin expression not identified
    • Individual contributions of EVL versus VASP to diapedesis not separated
  16. 2020 High

    CRISPR knockout of all three Ena/VASP proteins confirmed VASP as a positive regulator of lamellipodial assembly, demonstrating reduced filament length, abolished microspikes, impaired integrin adhesion, and reduced traction forces; separately, PKG/VASP Ser239 phosphorylation was linked to NF-κB suppression and NLRP3 inflammasome inhibition.

    Evidence Triple CRISPR KO with EM, traction force microscopy, and adhesion assays; PKG inhibitor and VASP phosphorylation analysis in Kupffer cells with NF-κB reporter

    PMID:32391788 PMID:33106416

    Open questions at the time
    • Whether triple KO phenotype reflects VASP-specific or family-wide loss not resolved
    • Whether VASP Ser239 directly binds NF-κB pathway components not tested
  17. 2022 High

    Full reconstitution of IRSp53-VASP membrane clusters showed they generate actin-filled protrusions resembling filopodia, and proteomic EVH1 domain profiling revealed noncanonical binding modes with extended SLiMs, expanding the known EVH1 interactome and structural logic.

    Evidence Liposome/SLB reconstitution with TIRF; proteomic peptide screen with X-ray crystallography of EVH1-peptide complexes

    PMID:35076015 PMID:36240267

    Open questions at the time
    • Whether noncanonical EVH1 binding modes apply to VASP (versus ENAH-specific) not directly tested
    • In vivo relevance of extended SLiM interactions not validated
  18. 2023 High

    VASP was shown to undergo liquid-liquid phase separation, with actin polymerization inside condensates driving filament partitioning to droplet edges and eventual deformation into parallel bundles, revealing a phase separation-based mechanism for organized actin bundle formation.

    Evidence In vitro phase separation assay, TIRF/confocal imaging, computational modeling comparing liquid versus solid droplet behavior

    PMID:38405682

    Open questions at the time
    • Whether VASP phase separation occurs in cells under physiological conditions not demonstrated
    • How phosphorylation regulates condensate formation unknown
    • Relationship between condensate-based bundling and filopodium formation in vivo not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The full-length structure of the VASP tetramer in complex with actin barbed ends remains undetermined, and how phosphorylation at multiple sites coordinately tunes processivity, partner switching, and phase separation behavior in vivo is unresolved.
  • No high-resolution structure of VASP tetramer bound to barbed end
  • Coordinated regulation by simultaneous multisite phosphorylation not systematically studied
  • In vivo evidence for VASP phase separation lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6 GO:0005198 structural molecule activity 4
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 4 GO:0005829 cytosol 1
Pathway
R-HSA-109582 Hemostasis 4 R-HSA-162582 Signal Transduction 4 R-HSA-1500931 Cell-Cell communication 2 R-HSA-168256 Immune System 2
Partners
CRKLIRSP53LPDNPFN1RIAMSPTAN1VINCULINZYXIN

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 VASP is a novel phosphoprotein that directly binds F-actin and associates with actin filaments and focal contact areas in human platelets and fibroblasts; it is stoichiometrically phosphorylated by both cGMP-dependent and cAMP-dependent protein kinases in intact human platelets. Subcellular fractionation, immunofluorescence, F-actin binding assay, in vivo phosphorylation in intact platelets The EMBO journal High 1318192
1995 VASP is a natural proline-rich ligand for profilins; it binds directly to purified profilins from human platelets, calf thymus, and birch pollen via its proline-rich domain, and co-localizes with profilin in living cells. Direct binding assay with purified proteins, profilin affinity chromatography, immunofluorescence co-localization The EMBO journal High 7737110
1995 VASP phosphorylation in intact platelets is regulated by serine/threonine protein phosphatases PP1 and PP2A, as demonstrated by okadaic acid-induced accumulation of phospho-VASP; PP1, PP2A, PP2B, and PP2C differ in selectivity for individual VASP phosphorylation sites in vitro. In vitro dephosphorylation assay with purified phosphatases, okadaic acid treatment of intact platelets, immunoblotting FEBS letters Medium 7656973
1996 VASP (and related Mena) associates with the surface of intracellular pathogen Listeria monocytogenes and with the G-actin binding protein profilin, implicating it in facilitating actin polymerization for bacterial movement; a conserved EVH1 domain targets Ena/VASP proteins to proline-rich motif-containing proteins. Co-localization immunofluorescence, pulldown/association assay, overexpression in fibroblasts Cell High 8861907
1996 VASP binds specifically to the proline-rich region of the focal adhesion protein vinculin (residues 839-850, proline-rich motif-1), identifying vinculin as a VASP-binding protein likely responsible for recruiting VASP to focal adhesions; the C-terminal EVH2 domain of VASP is required for vinculin binding. In vitro transcription/translation, GST-fusion protein pulldown, peptide binding assay The Biochemical journal High 8836115
1998 VASP-vinculin complexes can be immunoprecipitated from cell lysates; PIP2 greatly enhances VASP-vinculin complex formation by disrupting vinculin intramolecular head-tail interaction and inducing oligomerization; both the EVH1 and EVH2 domains of VASP participate in vinculin binding. Co-immunoprecipitation, in vitro binding assay with PIP2, immunofluorescence co-localization Current biology High 9560340
1999 VASP's EVH1 domain binds in high-affinity equilibrium to the proline-rich region of ActA (Listeria); VASP also interacts with F-actin via its C-terminal EVH2 domain, linking the bacterium to the actin tail required for movement; phosphorylation of Ser157 by PKA increases VASP affinity for F-actin ~40-fold (phospho-VASP Kd ~2×10^-8 M vs. dephospho-VASP 40-fold lower). In vitro motility assay (immunodepletion + add-back of recombinant VASP), quantitative binding assay, PKA phosphorylation in vitro The Journal of cell biology High 10087267
1999 Aromatic and basic residues within the EVH1 domain of VASP are required for binding to proline-rich ligands (ActA DFPPPPTD motif); charge-reversal mutations in the EVH1 domain abolish ActA binding, and complementary mutations in the ligand partially rescue binding, demonstrating a charged electrostatic specificity mechanism similar to SH3 domains. In vitro binding assays (three independent assays), site-directed mutagenesis of EVH1 domain, charge-reversal rescue experiment Current biology High 10498433
1999 VASP is required for cAMP- and cGMP-mediated inhibition of platelet aggregation but is dispensable for smooth muscle contraction and relaxation; VASP-deficient mice have normal smooth muscle function but significantly reduced cyclic nucleotide-mediated inhibition of platelet aggregation, while other cAMP/cGMP effects (calcium mobilization, granule secretion) remain VASP-independent. VASP gene knockout mouse model, platelet aggregation assay, calcium measurements, granule secretion assay, smooth muscle tension measurements The EMBO journal High 9878048
2000 Ena/VASP proteins negatively regulate fibroblast motility in a dose-dependent manner; selective depletion from focal adhesions (but not the leading edge) has no effect on motility, while constitutive membrane targeting of Ena/VASP proteins inhibits motility. Overexpression, loss-of-function (neutralization, deletion), selective depletion using domain-targeting constructs, cell migration assay Cell High 10892743
2001 VASP enhances Arp2/3 complex-mediated actin nucleation by ActA and simultaneously reduces the frequency of actin filament branch formation, demonstrating that VASP can generate distinct populations of actin filaments via both VASP-dependent and -independent Arp2/3 mechanisms. In vitro actin nucleation assay with purified VASP and Arp2/3 complex, genetic rescue with VASP in ActA mutants lacking actin monomer-binding region The Journal of cell biology High 11581288
2001 VASP interacts directly with the proline-rich domain of WASp (affinity ~10^6 M^-1); VASP and WASp co-accumulate in phagocytic cups; VASP enhances actin-based propulsion of WASp-coated beads in a reconstituted motility assay. In vitro binding assay (quantitative affinity measurement), co-localization immunofluorescence, reconstituted bead motility assay The EMBO journal High 11598004
2002 Ena/VASP proteins associate with barbed ends of actin filaments and shield them from capping protein (CapZ), promoting filament elongation; Ena/VASP-deficient lamellipodia contain shorter, more highly branched filaments, while excess Ena/VASP produces longer, less branched filaments. In vitro barbed-end capping assay with purified proteins, electron microscopy of actin networks, loss-of-function and overexpression in fibroblasts, live cell imaging Cell High 12086607
2002 Cyclic nucleotide-dependent kinase phosphorylation sites and the F-actin binding motif (EVH2 domain) are essential for VASP/Mena function in random cell motility; profilin-binding (proline-rich central region) is dispensable for motility regulation; the EVH2 domain alone is sufficient to complement loss of Ena/VASP function. Complementation of Ena/VASP-deficient cells with site-directed mutants, cell migration assay, domain deletion analysis Molecular biology of the cell High 12134088
2002 For Listeria motility, the proline-rich region and Ser/Thr phosphorylation sites of VASP are required for efficient bacterial movement, while F-actin binding and multimerization are dispensable; VASP contributes to both nucleation and elongation of actin filaments at the bacterial surface. Expression of Ena/VASP mutants in Ena/VASP-deficient cells, Listeria motility assay, domain deletion and phosphorylation-site mutagenesis Molecular biology of the cell High 12134077
2003 In vivo, VASP-deficient mice show significantly enhanced platelet adhesion to endothelial cells under physiologic and pathophysiologic conditions; platelet adhesion in VASP-null mice is unresponsive to nitric oxide, placing VASP downstream of the NO signaling pathway for inhibition of platelet-vessel wall interactions. VASP-knockout mouse intravital microscopy, platelet adhesion assay, pharmacological NO manipulation Blood High 12933589
2003 Displacement of both VASP and Mena from cardiac intercalated disks (by cardiac-specific overexpression of the EVH1 domain) causes dilated cardiomyopathy with myocyte hypertrophy and early lethality, demonstrating that Ena/VASP proteins are required for intercalated disk function. Transgenic mice with cardiac-specific EVH1 domain overexpression (dominant-negative), histopathology, echocardiography American journal of physiology. Heart and circulatory physiology Medium 12933343
2004 VASP is identified as a binding partner of Lamellipodin (Lpd); both proteins co-localize at tips of lamellipodia and filopodia; Lpd overexpression increases lamellipodial protrusion velocity in an Ena/VASP-dependent manner. Co-immunoprecipitation, co-localization, Lpd knockdown, overexpression rescue assay Developmental cell High 15469845
2004 RIAM interacts with Ena/VASP proteins (and Profilin) via its proline-rich motifs; RIAM overexpression induces lamellipodia formation and integrin activation in an actin-polymerization-dependent manner, linking Rap1-GTP signaling to Ena/VASP-mediated actin dynamics. Co-immunoprecipitation, yeast two-hybrid, overexpression and knockdown phenotype, cell adhesion assay Developmental cell High 15469846
2004 Myosin X binds to Mena/VASP and transports it from the root to the tip of filopodia; the amount of VASP at filopodial tips is proportional to Myosin X levels, and co-movement of EGFP-M10 and RFP-VASP was directly visualized in living cells. Co-immunoprecipitation, immunocytochemistry co-localization, live-cell fluorescence imaging of dual-labeled proteins Biochemical and biophysical research communications Medium 15158464
2006 Zyxin recruits Ena/VASP proteins to focal adhesions; zyxin-null fibroblasts show severely reduced accumulation of Ena/VASP proteins at focal adhesions, increased motility, and deficits in actin stress fiber remodeling. Zyxin gene knockout by homologous recombination, immunofluorescence, cell migration assay, mass spectrometry The Journal of cell biology High 16505170
2006 PKCδ physically interacts with VASP constitutively and negatively regulates its phosphorylation at Ser157; PKCδ-deficient platelets show enhanced filopodia formation and platelet aggregation that is ablated in VASP-deficient platelets, placing VASP downstream of PKCδ in filopodia regulation. Co-immunoprecipitation of PKCδ-VASP, PKCδ-/- and VASP-/- mouse platelets, pharmacological rottlerin treatment, actin polymerization assay Blood High 16940418
2007 αII-Spectrin binds to VASP via its SH3 domain interacting with the VASP triple GP(5)-motif; PKA-mediated VASP phosphorylation at Ser157 inhibits αII-spectrin-VASP binding; upon cell-cell contact formation, dephosphorylated VASP colocalizes with αII-spectrin at junctions; αII-spectrin-VASP complexes regulate cortical actin assembly and endothelial barrier function. Differential proteomics, co-immunoprecipitation, phosphorylation-state-dependent binding assay, ectopic domain expression, VASP-KO endothelial cells, permeability assay in VASP-null mice The Journal of cell biology High 18195108
2007 NO-stimulated cGMP-dependent protein kinase (PKG type II) phosphorylates VASP Ser239 in primary cells; phosphorylation at Ser239 causes rapid lamellipodial retraction and cell rounding; VASP Ser239Ala mutant is unresponsive to NO, demonstrating that Ser239 phosphorylation inhibits lamellipodial actin polymerization. Live-cell imaging of GFP-VASP constructs, site-directed mutagenesis (Ser239Ala), NO stimulation, guanylate cyclase inhibitors Journal of cell science High 17684063
2007 Syndecan-2 activates PKA via neurofibromin (a syndecan-2 binding partner that activates cAMP pathway), which then phosphorylates Ena/VASP proteins to promote actin polymerization, filopodia formation, and dendritic spine formation; blocking Ena/VASP activity abolishes syndecan-2-induced filopodia. Kinase inhibitor screening, deletion mutant analysis, RNA interference, dominant-negative constructs The Journal of cell biology Medium 17548511
2008 Clustered VASP (on functionalized beads) switches to processive filament elongation that becomes insensitive even to high concentrations of capping protein; this requires VASP WH2 domains for G-actin delivery to the barbed end; solution-phase VASP accelerates elongation in a concentration-dependent manner but is inhibited by low concentrations of capping protein. In vitro TIRF microscopy, VASP-coated bead motility assay, VASP WH2 domain mutagenesis, EM structure The EMBO journal High 18923426
2010 Lamellipodin (Lpd) is phosphorylated by Abl kinases; Lpd phosphorylation positively regulates the Lpd-Ena/VASP interaction and promotes recruitment of Mena/EVL to the leading edge, placing Abl upstream of Lpd-Ena/VASP in dorsal ruffling and axonal morphogenesis. In vitro kinase assay, Abl SH2 domain binding assay, co-immunoprecipitation, PDGF and netrin-1 stimulation of primary neurons, dominant-negative Abl Current biology High 20417104
2010 αvβ3 integrin regulates PKA-dependent phosphorylation of VASP; in β3-null fibroblasts, dephosphorylated VASP preferentially associates with RIAM both in vitro and in vivo, forming a VASP-RIAM complex at focal adhesions that enhances talin-β1 integrin binding, thus αvβ3 suppresses β1 integrin activation through PKA/VASP/RIAM pathway. β3-integrin KO fibroblasts, in vitro pull-down (VASP-RIAM interaction), phosphorylation analysis, cell migration assay The Journal of cell biology Medium 20404115
2011 VASP-mediated actin filament elongation rate is determined by G-actin recruitment via the WH2 (WASP homology 2) motif; VASP-mediated elongation displays saturation dependence on actin monomer concentration, implying VASP is fully saturated with actin in vivo; spontaneous addition of monomers does not occur during processive VASP-mediated elongation. In vitro TIRF microscopy of chimeric VASP proteins, thermodynamic and kinetic analyses, quantitative mathematical modeling The EMBO journal High 21217643
2011 AMPK phosphorylates VASP at a novel site, serine 322 (distinct from the well-characterized PKA/PKG sites Ser157, Ser239, Thr278); phosphorylation at Ser322 alters actin filament binding; inhibition of AMPK leads to accumulation of VASP at cell-cell adhesions and increased cell-cell adhesion. In vitro AMPK kinase assay, mass spectrometry phosphosite identification, actin-binding assay, AMPK inhibitor treatment Biochemical and biophysical research communications Medium 21945940
2012 VASP ablation increases Rac1 activation, which upregulates soluble guanylyl cyclase (sGC) abundance, increasing cGMP production; this VASP→Rac1→sGC negative feedback loop limits cGMP levels and adipogenesis; VASP-deficient mice show increased energy expenditure and brown adipocyte differentiation. VASP knockout mouse and cells, Rac1 activity assay, sGC protein quantification, cGMP measurement, brown adipocyte differentiation assay Science signaling Medium 22932701
2013 CDC42-activated IRSp53 recruits VASP and promotes high-density VASP clustering, which is required for processive actin filament elongation and filopodium initiation; without CDC42 activation, IRSp53 inhibits actin barbed-end growth; the IRSp53-VASP interaction is regulated by CDC42 and mediates VASP recruitment to liposomes. In vitro TIRF actin polymerization assay, liposome recruitment assay, IRSp53 and CDC42 genetic manipulation, TIRF imaging of barbed-end dynamics The EMBO journal High 24076653
2014 Drosophila Ena (an Ena/VASP ortholog) is a highly processive actin polymerase that processively associates with barbed ends (~10–110 s depending on surface clustering); Ena tetramers increase elongation rate 2-3 fold, inhibit capping protein, and on Fascin-bundled filaments display ~2-fold more frequent and ~5-fold longer processive runs, allowing trailing barbed ends to catch up. Multicolor evanescent-wave (TIRF) fluorescence microscopy of individual Ena molecules, in vitro actin polymerization assay, Fascin-bundled filament assay Proceedings of the National Academy of Sciences High 24591594
2014 Palladin recruits VASP to dorsal stress fibers via direct binding through palladin's proline-rich amino-terminal domain; this interaction is required for assembly of non-contractile dorsal stress fibers; both proteins show rapid co-dynamics at dorsal stress fibers suggesting they associate as a complex. Palladin knockdown, Co-immunoprecipitation, FRAP, live-cell imaging, 3D cell migration assay Journal of cell science High 24496446
2015 Lamellipodin (Lpd) binds directly to actin filaments; this interaction regulates Lpd subcellular localization and enhances VASP polymerase activity; Lpd delivers Ena/VASP proteins to growing barbed ends and increases their polymerase activity by tethering them to filaments. In vitro actin filament binding assay (direct binding of purified Lpd), in vitro TIRF actin polymerization assay, in vivo localization studies eLife High 26295568
2015 VASP Ser157 phosphorylation mediates its membrane localization in airway smooth muscle; interaction of VASP with activated vinculin at membrane adhesion sites is a necessary prerequisite for VASP-mediated actin polymerization and tension generation during contractile activation; VASP-VASP, VASP-vinculin, and VASP-profilin complexes form at membrane sites in response to acetylcholine. VASP S157A mutant expression in smooth muscle tissue, co-immunoprecipitation (VASP-VASP, VASP-vinculin, VASP-profilin), inactive vinculin mutant (Y1065F) expression, tension measurement The Journal of biological chemistry Medium 25759389
2016 VASP interacts directly with CRKL via the N-terminal SH3 domain of CRKL; PKA-mediated VASP phosphorylation at Ser157 abrogates CRKL binding; the C3G/CRKL/VASP complex regulates Rap1b activation in platelets, explaining reduced agonist-induced Rap1b activation in VASP-null platelets. Co-immunoprecipitation, confocal co-localization, GST-CRKL domain pulldown with recombinant VASP, Rap1b activation assay (GST-RalGDS-RBD), VASP-KO platelets Cell communication and signaling High 27620165
2017 EVL and VASP are required for activated T-cell diapedesis (transendothelial migration) and regulate α4 integrin (CD49d) expression and function; EVL/VASP double-KO T cells show normal shear-resistant adhesion and crawling but impaired diapedesis that is restored by α4 integrin blockade. EVL/VASP double-knockout mice, intravital microscopy, transendothelial migration assay under shear, EAE model, α4 integrin blockade Proceedings of the National Academy of Sciences High 28320969
2020 CRISPR/Cas9-mediated loss of all Ena/VASP proteins reduces lamellipodial actin assembly, shortens filament length and number, causes abnormal Arp2/3 complex and capping protein distribution, abolishes microspike formation, impairs integrin-mediated adhesion, and reduces traction forces, demonstrating VASP as a positive regulator of cell migration. CRISPR/Cas9 triple knockout, electron microscopy of actin networks, traction force microscopy, Arp2/3/CP localization, integrin adhesion assay eLife High 32391788
2020 PKG-mediated phosphorylation of VASP Ser239 reduces NF-κB activity and inhibits Il1b and Nlrp3 gene transcription in Kupffer cells, establishing a sGC/PKG/VASP/NF-κB/NLRP3 inflammasome circuit for hepatic anti-inflammatory signaling. PKG inhibitor, VASP Ser239 phosphorylation analysis, NF-κB reporter assay, NLRP3 inflammasome component measurement, LPS+ATP Kupffer cell model Proceedings of the National Academy of Sciences Medium 33106416
2022 Full-length IRSp53 self-assembles into PIP2-dependent clusters on membranes that recruit VASP; reconstituted IRSp53 clusters assemble actin filaments via VASP locally on membranes, generating actin-filled membrane protrusions resembling filopodia; VASP is only enriched and triggers actin assembly in highly dynamic membrane nanotubes in live cells. In vitro reconstitution on membranes (liposomes/SLBs), TIRF microscopy, live-cell membrane nanotube pulling assay, in cellulo experiments Science advances High 36240267
2023 VASP forms liquid-like droplets under physiological conditions; as actin polymerizes within VASP condensates, elongating filaments partition to droplet edges forming an actin ring, whose growing rigidity eventually overcomes droplet surface tension to deform into a parallel-bundled actin bundle; the fluid nature of the droplets is critical for filament rearrangement and bundling. In vitro phase separation assay, TIRF and confocal fluorescence microscopy, continuum-scale computational modeling, comparison of liquid vs. solid droplet conditions Nature physics High 38405682
2007 VASP is identified as a direct interacting protein with CXCR2; the interaction is enhanced by CXCL8 stimulation, which triggers VASP phosphorylation via PKA- and PKCδ-mediated pathways; interaction requires free F-actin barbed ends; VASP knockdown severely impairs CXCR2-mediated chemotaxis and neutrophil polarization. Proteomics pulldown, direct interaction assay, phosphorylation analysis, VASP siRNA knockdown, chemotaxis assay Journal of cell science Medium 19435808
2007 PKG-phosphorylated VASP (at Ser239) associates with TRPC4 (a store-operated calcium channel component) in mesangial cells; unphosphorylated VASP does not associate with TRPC4; this VASP-TRPC4 interaction mediates NO/PKG-dependent inhibition of the store-operated calcium response. Co-immunoprecipitation with phospho-specific antibodies, immunocytochemistry co-localization, 8-Br-cGMP stimulation, PKG inhibitor (DT-3) American journal of physiology. Renal physiology Medium 17913834
2022 The ENAH EVH1 domain contains a pocket diverged from other Ena/VASP paralogs that recognizes extended SLiMs with motif-flanking proline residues; many high-affinity binders engage a noncanonical site on the EVH1 domain with two proline-rich SLiMs; PCARE uses an extended 23-residue region achieving higher affinity than any known EVH1-binding motif. Proteomic peptide screen (36-residue proteome-derived peptides), X-ray crystallography of EVH1-inhibitor complexes, quantitative binding assays eLife High 35076015

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Antagonism between Ena/VASP proteins and actin filament capping regulates fibroblast motility. Cell 682 12086607
1996 Mena, a relative of VASP and Drosophila Enabled, is implicated in the control of microfilament dynamics. Cell 574 8861907
2003 Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration. Annual review of cell and developmental biology 541 14570581
1995 The proline-rich focal adhesion and microfilament protein VASP is a ligand for profilins. The EMBO journal 405 7737110
2000 Negative regulation of fibroblast motility by Ena/VASP proteins. Cell 395 10892743
2004 RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion. Developmental cell 334 15469846
1992 The 46/50 kDa phosphoprotein VASP purified from human platelets is a novel protein associated with actin filaments and focal contacts. The EMBO journal 320 1318192
1999 Role of proteins of the Ena/VASP family in actin-based motility of Listeria monocytogenes. The Journal of cell biology 283 10087267
1999 The vasodilator-stimulated phosphoprotein (VASP) is involved in cGMP- and cAMP-mediated inhibition of agonist-induced platelet aggregation, but is dispensable for smooth muscle function. The EMBO journal 274 9878048
2004 Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics. Developmental cell 262 15469845
1999 Flow cytometry analysis of intracellular VASP phosphorylation for the assessment of activating and inhibitory signal transduction pathways in human platelets--definition and detection of ticlopidine/clopidogrel effects. Thrombosis and haemostasis 251 10494779
2008 Clustering of VASP actively drives processive, WH2 domain-mediated actin filament elongation. The EMBO journal 191 18923426
2001 Actin-based motility: stop and go with Ena/VASP proteins. Trends in biochemical sciences 168 11295557
1996 The focal-adhesion vasodilator-stimulated phosphoprotein (VASP) binds to the proline-rich domain in vinculin. The Biochemical journal 168 8836115
2001 Evidence for a molecular complex consisting of Fyb/SLAP, SLP-76, Nck, VASP and WASP that links the actin cytoskeleton to Fcgamma receptor signalling during phagocytosis. Journal of cell science 164 11739662
2004 Myosin X transports Mena/VASP to the tip of filopodia. Biochemical and biophysical research communications 143 15158464
2018 Hypoxia-induced up-regulation of VASP promotes invasiveness and metastasis of hepatocellular carcinoma. Theranostics 139 30279729
2006 Genetic ablation of zyxin causes Mena/VASP mislocalization, increased motility, and deficits in actin remodeling. The Journal of cell biology 137 16505170
1998 The interaction of the cell-contact proteins VASP and vinculin is regulated by phosphatidylinositol-4,5-bisphosphate. Current biology : CB 135 9560340
2003 Function and regulation of Ena/VASP proteins. Trends in cell biology 132 12837609
2014 Ena/VASP Enabled is a highly processive actin polymerase tailored to self-assemble parallel-bundled F-actin networks with Fascin. Proceedings of the National Academy of Sciences of the United States of America 126 24591594
2011 Molecular mechanism of Ena/VASP-mediated actin-filament elongation. The EMBO journal 126 21217643
2007 Syndecan-2 induces filopodia and dendritic spine formation via the neurofibromin-PKA-Ena/VASP pathway. The Journal of cell biology 116 17548511
2002 Critical roles of phosphorylation and actin binding motifs, but not the central proline-rich region, for Ena/vasodilator-stimulated phosphoprotein (VASP) function during cell migration. Molecular biology of the cell 112 12134088
2011 Endothelial NO/cGMP/VASP signaling attenuates Kupffer cell activation and hepatic insulin resistance induced by high-fat feeding. Diabetes 111 21911751
2001 Pivotal role of VASP in Arp2/3 complex-mediated actin nucleation, actin branch-formation, and Listeria monocytogenes motility. The Journal of cell biology 106 11581288
2013 CDC42 switches IRSp53 from inhibition of actin growth to elongation by clustering of VASP. The EMBO journal 98 24076653
2008 Cytoskeleton assembly at endothelial cell-cell contacts is regulated by alphaII-spectrin-VASP complexes. The Journal of cell biology 98 18195108
2003 Enhanced in vivo platelet adhesion in vasodilator-stimulated phosphoprotein (VASP)-deficient mice. Blood 98 12933589
1993 Role of cyclic nucleotide-dependent protein kinases and their common substrate VASP in the regulation of human platelets. Advances in experimental medicine and biology 97 8209791
2001 A WASp-VASP complex regulates actin polymerization at the plasma membrane. The EMBO journal 92 11598004
2006 PKCdelta regulates collagen-induced platelet aggregation through inhibition of VASP-mediated filopodia formation. Blood 88 16940418
2007 The role of VASP in regulation of cAMP- and Rac 1-mediated endothelial barrier stabilization. American journal of physiology. Cell physiology 82 17989211
2002 Role of VASP in reestablishment of epithelial tight junction assembly after Ca2+ switch. American journal of physiology. Cell physiology 81 11997237
2002 Contribution of Ena/VASP proteins to intracellular motility of listeria requires phosphorylation and proline-rich core but not F-actin binding or multimerization. Molecular biology of the cell 81 12134077
1999 Aromatic and basic residues within the EVH1 domain of VASP specify its interaction with proline-rich ligands. Current biology : CB 79 10498433
2006 Unusual splicing events result in distinct Xin isoforms that associate differentially with filamin c and Mena/VASP. Experimental cell research 78 16631741
2008 A comparison of the antiplatelet effects of prasugrel and high-dose clopidogrel as assessed by VASP-phosphorylation and light transmission aggregometry. Thrombosis and haemostasis 77 18217157
2004 Palladin is a novel binding partner for Ena/VASP family members. Cell motility and the cytoskeleton 75 14983521
2020 Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion. eLife 74 32391788
2016 Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE. Oncogene 74 26996666
2009 Loss of profilin-1 expression enhances breast cancer cell motility by Ena/VASP proteins. Journal of cellular physiology 71 19115233
2005 WASP-related proteins, Abi1 and Ena/VASP are required for Listeria invasion induced by the Met receptor. Journal of cell science 70 15769844
2015 Lamellipodin promotes actin assembly by clustering Ena/VASP proteins and tethering them to actin filaments. eLife 69 26295568
2010 c-Abl, Lamellipodin, and Ena/VASP proteins cooperate in dorsal ruffling of fibroblasts and axonal morphogenesis. Current biology : CB 69 20417104
2010 Alpha v beta3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration. The Journal of cell biology 67 20404115
2008 Relaxing the actin cytoskeleton for adhesion and movement with Ena/VASP. The Journal of cell biology 64 18378777
2002 The WH1 and EVH1 domains of WASP and Ena/VASP family members bind distinct sequence motifs. Current biology : CB 60 12372256
2014 Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function. Molecular biology of the cell 56 24989797
2003 Phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) by the anti-platelet drug, cilostazol, in platelets. Platelets 55 14602552
2022 Ena/VASP proteins in cell edge protrusion, migration and adhesion. Journal of cell science 54 35285496
2020 Stimulation of soluble guanylate cyclase exerts antiinflammatory actions in the liver through a VASP/NF-κB/NLRP3 inflammasome circuit. Proceedings of the National Academy of Sciences of the United States of America 54 33106416
2007 Identification of vasodilator-stimulated phosphoprotein (VASP) as an HIF-regulated tissue permeability factor during hypoxia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 54 17412998
2020 Interleukin 1β-mediated HOXC10 Overexpression Promotes Hepatocellular Carcinoma Metastasis by Upregulating PDPK1 and VASP. Theranostics 52 32206125
2009 VASP is a CXCR2-interacting protein that regulates CXCR2-mediated polarization and chemotaxis. Journal of cell science 52 19435808
2003 Ena/VASP proteins contribute to Listeria monocytogenes pathogenesis by controlling temporal and spatial persistence of bacterial actin-based motility. Molecular microbiology 52 12940993
2020 Arp2/3 and Mena/VASP Require Profilin 1 for Actin Network Assembly at the Leading Edge. Current biology : CB 51 32470361
2005 Differential expression of VASP in normal lung tissue and lung adenocarcinomas. Thorax 49 15994266
2011 The Eps8/IRSp53/VASP network differentially controls actin capping and bundling in filopodia formation. PLoS computational biology 48 21814501
2007 Modulation of lamellipodial structure and dynamics by NO-dependent phosphorylation of VASP Ser239. Journal of cell science 48 17684063
2003 Endothelium-dependent and -independent relaxation and VASP serines 157/239 phosphorylation by cyclic nucleotide-elevating vasodilators in rat aorta. Biochemical pharmacology 48 12527332
1995 Dephosphorylation of the focal adhesion protein VASP in vitro and in intact human platelets. FEBS letters 48 7656973
2023 Liquid-like VASP condensates drive actin polymerization and dynamic bundling. Nature physics 47 38405682
2013 Regulation of VASP by phosphorylation: consequences for cell migration. Cell adhesion & migration 46 24401601
2005 PREL1 provides a link from Ras signalling to the actin cytoskeleton via Ena/VASP proteins. FEBS letters 45 15642358
2014 TNF-α mediated increase of HIF-1α inhibits VASP expression, which reduces alveolar-capillary barrier function during acute lung injury (ALI). PloS one 43 25051011
1998 The focal adhesion phosphoprotein, VASP. The international journal of biochemistry & cell biology 42 9611773
2020 ITGA3 interacts with VASP to regulate stemness and epithelial-mesenchymal transition of breast cancer cells. Gene 41 31987909
2006 Regulation of somitogenesis by Ena/VASP proteins and FAK during Xenopus development. Development (Cambridge, England) 41 16421193
2019 The Wnt/β-catenin/VASP positive feedback loop drives cell proliferation and migration in breast cancer. Oncogene 38 31831834
2017 Ena/VASP proteins regulate activated T-cell trafficking by promoting diapedesis during transendothelial migration. Proceedings of the National Academy of Sciences of the United States of America 38 28320969
2022 Activated I-BAR IRSp53 clustering controls the formation of VASP-actin-based membrane protrusions. Science advances 36 36240267
2009 Inflammation-associated repression of vasodilator-stimulated phosphoprotein (VASP) reduces alveolar-capillary barrier function during acute lung injury. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 36 19690214
2008 Role of Ena/VASP proteins in homeostasis and disease. Handbook of experimental pharmacology 36 18491048
2003 Disruption of cardiac Ena-VASP protein localization in intercalated disks causes dilated cardiomyopathy. American journal of physiology. Heart and circulatory physiology 36 12933343
2016 Vasodilator-Stimulated Phosphoprotein (VASP)-dependent and -independent pathways regulate thrombin-induced activation of Rap1b in platelets. Cell communication and signaling : CCS 35 27620165
2020 Initiation and disassembly of filopodia tip complexes containing VASP and lamellipodin. Molecular biology of the cell 34 32579429
2016 Fat3 and Ena/VASP proteins influence the emergence of asymmetric cell morphology in the developing retina. Development (Cambridge, England) 34 27122175
2009 Role of VASP phosphorylation for the regulation of microglia chemotaxis via the regulation of focal adhesion formation/maturation. Molecular and cellular neurosciences 34 19733667
2014 Palladin promotes assembly of non-contractile dorsal stress fibers through VASP recruitment. Journal of cell science 32 24496446
2009 Impaired integrin-mediated adhesion contributes to reduced barrier properties in VASP-deficient microvascular endothelium. Journal of cellular physiology 30 19347869
2015 Vasodilator-stimulated phosphoprotein (VASP) regulates actin polymerization and contraction in airway smooth muscle by a vinculin-dependent mechanism. The Journal of biological chemistry 29 25759389
2010 VASP: a volumetric analysis of surface properties yields insights into protein-ligand binding specificity. PLoS computational biology 29 20814581
2005 VASP-dependent regulation of actin cytoskeleton rigidity, cell adhesion, and detachment. Histochemistry and cell biology 29 16267652
2017 Vasodilator-Stimulated Phosphoprotein (VASP) depletion from breast cancer MDA-MB-231 cells inhibits tumor spheroid invasion through downregulation of Migfilin, β-catenin and urokinase-plasminogen activator (uPA). Experimental cell research 28 28209486
2016 Tumor suppressor berberine binds VASP to inhibit cell migration in basal-like breast cancer. Oncotarget 28 27322681
2013 Matrine inhibits the adhesion and migration of BCG823 gastric cancer cells by affecting the structure and function of the vasodilator-stimulated phosphoprotein (VASP). Acta pharmacologica Sinica 28 23685951
2012 A phosphatidylinositol lipids system, lamellipodin, and Ena/VASP regulate dynamic morphology of multipolar migrating cells in the developing cerebral cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 28 22915108
2012 A VASP-Rac-soluble guanylyl cyclase pathway controls cGMP production in adipocytes. Science signaling 28 22932701
2019 Silencing lncRNA SNHG6 suppresses proliferation and invasion of breast cancer cells through miR-26a/VASP axis. Pathology, research and practice 27 31387807
2014 VASP activation via the Gα13/RhoA/PKA pathway mediates cucurbitacin-B-induced actin aggregation and cofilin-actin rod formation. PloS one 27 24691407
2011 Phosphorylation of VASP by AMPK alters actin binding and occurs at a novel site. Biochemical and biophysical research communications 27 21945940
2007 Association of VASP with TRPC4 in PKG-mediated inhibition of the store-operated calcium response in mesangial cells. American journal of physiology. Renal physiology 27 17913834
2022 Native proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH. eLife 26 35076015
2007 Regulation of VASP serine 157 phosphorylation in human neutrophils after stimulation by a chemoattractant. Journal of leukocyte biology 26 17684042
2020 Designed nanomolar small-molecule inhibitors of Ena/VASP EVH1 interaction impair invasion and extravasation of breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America 25 33184177
2018 Roles for Ena/VASP proteins in FMNL3-mediated filopodial assembly. Journal of cell science 25 30373894
2017 Role of NO/VASP Signaling Pathway against Obesity-Related Inflammation and Insulin Resistance. Diabetes & metabolism journal 25 28447436
2000 The vasodilator-stimulated phosphoprotein (VASP): target of YC-1 and nitric oxide effects in human and rat platelets. Journal of cardiovascular pharmacology 25 10710123
2019 CREB1/Lin28/miR-638/VASP Interactive Network Drives the Development of Breast Cancer. International journal of biological sciences 24 31754343