The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

VASP  -  vasodilator-stimulated phosphoprotein

Homo sapiens

Synonyms: Vasodilator-stimulated phosphoprotein
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of VASP


High impact information on VASP

  • Putting on the brakes: a negative regulatory function for Ena/VASP proteins in cell migration [5].
  • Structure of the enabled/VASP homology 1 domain-peptide complex: a key component in the spatial control of actin assembly [6].
  • Phosphorylation by these kinases appears to modulate Ena/VASP function within cells, although the mechanism underlying this regulation remains to be determined [7].
  • Ena/VASP proteins are a conserved family of actin regulatory proteins made up of EVH1, EVH2 domains, and a proline-rich central region [7].
  • Vertebrate Ena/VASP proteins are substrates for PKA/PKG serine/threonine kinases [7].

Chemical compound and disease context of VASP


Biological context of VASP

  • The Ena-VASP family of proteins act as molecular adaptors linking the cytoskeletal system to signal transduction pathways [11].
  • VASP-deficient mice may provide an interesting model system for diseases in which enhanced platelet activation plays a major role [3].
  • Hence, phosphorylation may significantly alter the actin binding properties of VASP [12].
  • Ena/VASP (enabled/vasodilator-stimulated phosphoprotein) proteins play an important role in actin and filament dynamics, whereas members of the semaphorin protein family are guidance signals in embryo- and organogenesis [13].
  • Thus, our data pinpoint PREL1 as the first direct link between Ras signalling and cytoskeletal remodelling via Ena/VASP proteins during cell migration and spreading [14].

Anatomical context of VASP

  • VASP is a microfilament and focal adhesion associated protein which is also concentrated in highly dynamic regions of the cell cortex [15].
  • Inhibition of binding between Fyb/SLAP and Ena/VASP proteins or WASP and the Arp2/3 complex impairs TCR-dependent actin rearrangement, suggesting that these interactions play a key role in linking T cell signaling to remodeling of the actin cytoskeleton [16].
  • In activated T cells, Fyb/SLAP associates with Ena/VASP family proteins and is present within biochemical complexes containing WASP, Nck, and SLP-76 [16].
  • Human platelet VASP bound directly to purified profilins from human platelets, calf thymus and birch pollen [15].
  • Ena/VASP proteins influence the organization of actin filament networks within lamellipodia and filopodia of migrating cells and in actin comet tails [17].

Associations of VASP with chemical compounds


Physical interactions of VASP


Enzymatic interactions of VASP

  • VASP is a major substrate for cAMP- and cGMP-regulated protein kinases and it has been shown to be directly phosphorylated on Ser157 by PKC (protein kinase C) [26].

Co-localisations of VASP

  • Immunofluorescence studies revealed that the two host proteins, VASP and (&agr;)-actinin colocalized with actin in the tails of Rickettsia but neither the Arp2/3 complex which we detected in the Shigella actin tails, nor N-WASP, were detected in Rickettsia actin tails [27].

Regulatory relationships of VASP

  • In addition, one of the effects of VEGF and IL-8 in angiogenesis may be to induce VASP expression in a paracrine manner [28].
  • These phenotypes are more severe than loss of Ena/VASP, suggesting that Lpd regulates other effectors of the actin cytoskeleton in addition to Ena/VASP [29].
  • Finally, in a reconstituted motility medium, VASP enhances actin-based propulsion of WASp-coated beads in a fashion reminiscent of its effect on Listeria movement [24].
  • WASP- and Ena/VASP-family proteins have been reported to regulate the cortical actin cytoskeleton as downstream effectors of the Rho-family small G-proteins Rac and Cdc42, but their functions are little understood [30].
  • In cultured cells, mammalian MIG-10 promotes lamellipodial growth and Ena/VASP proteins induce filopodia [31].

Other interactions of VASP

  • VASP, in turn, provides the ABM-2 sequences [XPPPPP, X = G, P, L, S, A] for binding profilin, an actin-regulatory protein that stimulates actin filament assembly [2].
  • Vinculin did not colocalize with VASP on motile virions and remained in focal adhesion contacts; however, another ABM-1-containing host protein, zyxin, was concentrated at the rear of motile virions [2].
  • The COOH-terminal half recruits zyxin as well as Mena and VASP from cell extracts [32].
  • LPP localizes in focal adhesions as well as in cell-to-cell contacts, and it binds VASP, a protein implicated in the control of actin organization [33].
  • Infections of either N-WASP- or Ena/VASP-defective cells showed that these proteins are not essential for B. pseudomallei-induced actin polymerization [34].

Analytical, diagnostic and therapeutic context of VASP

  • Determination of the VASP EVH1 domain solution structure, together with peptide library screening, measurement of individual K(d)s by fluorescence titration, and NMR chemical shift mapping, revealed a second affinity-determining epitope present in all four ActA EVH1-binding motifs [11].
  • VASP binding to purified p83 in solid-phase binding assays and the closely matching subcellular localization in double-label immunofluorescence analyses demonstrated that both proteins also directly interact as native proteins in vitro and possibly in living cells [22].
  • Using cosmid DNA as a probe for fluorescence in situ hybridization, the human VASP gene was assigned to chromosome 19q13.2-q13.3, an extended region with homology to mouse chromosome 7 [35].
  • Immunocytochemistry revealed that endogenous M10 co-localized with Mena/VASP at the tip of filopodia [36].
  • Here, we demonstrate that palladin is an additional direct binding partner for VASP, by using co-immunoprecipitation and blot overlay techniques with both endogenous palladin and recombinant myc-tagged palladin [37].


  1. A novel proline-rich motif present in ActA of Listeria monocytogenes and cytoskeletal proteins is the ligand for the EVH1 domain, a protein module present in the Ena/VASP family. Niebuhr, K., Ebel, F., Frank, R., Reinhard, M., Domann, E., Carl, U.D., Walter, U., Gertler, F.B., Wehland, J., Chakraborty, T. EMBO J. (1997) [Pubmed]
  2. Vaccinia locomotion in host cells: evidence for the universal involvement of actin-based motility sequences ABM-1 and ABM-2. Zeile, W.L., Condit, R.C., Lewis, J.I., Purich, D.L., Southwick, F.S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. Megakaryocyte hyperplasia and enhanced agonist-induced platelet activation in vasodilator-stimulated phosphoprotein knockout mice. Hauser, W., Knobeloch, K.P., Eigenthaler, M., Gambaryan, S., Krenn, V., Geiger, J., Glazova, M., Rohde, E., Horak, I., Walter, U., Zimmer, M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  4. Regulation of human endothelial cell focal adhesion sites and migration by cGMP-dependent protein kinase I. Smolenski, A., Poller, W., Walter, U., Lohmann, S.M. J. Biol. Chem. (2000) [Pubmed]
  5. Putting on the brakes: a negative regulatory function for Ena/VASP proteins in cell migration. Machesky, L.M. Cell (2000) [Pubmed]
  6. Structure of the enabled/VASP homology 1 domain-peptide complex: a key component in the spatial control of actin assembly. Prehoda, K.E., Lee, D.J., Lim, W.A. Cell (1999) [Pubmed]
  7. Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration. Krause, M., Dent, E.W., Bear, J.E., Loureiro, J.J., Gertler, F.B. Annu. Rev. Cell Dev. Biol. (2003) [Pubmed]
  8. Vasodilator-stimulated phosphoprotein (VASP) phosphorylation provides a biomarker for the action of exisulind and related agents that activate protein kinase G. Deguchi, A., Soh, J.W., Li, H., Pamukcu, R., Thompson, W.J., Weinstein, I.B. Mol. Cancer Ther. (2002) [Pubmed]
  9. Comparison of vasodilatory prostaglandins with respect to cAMP-mediated phosphorylation of a target substrate in intact human platelets. Nolte, C., Eigenthaler, M., Schanzenbächer, P., Walter, U. Biochem. Pharmacol. (1991) [Pubmed]
  10. Platelet VASP phosphorylation assessment in clopidogrel-treated patients: lack of agreement between Western blot and flow cytometry. Hezard, N., Metz, D., Garnotel, R., Simon, G., Mace, C., Koebel, P., Nguyen, P. Platelets (2005) [Pubmed]
  11. Dual epitope recognition by the VASP EVH1 domain modulates polyproline ligand specificity and binding affinity. Ball, L.J., Kühne, R., Hoffmann, B., Häfner, A., Schmieder, P., Volkmer-Engert, R., Hof, M., Wahl, M., Schneider-Mergener, J., Walter, U., Oschkinat, H., Jarchau, T. EMBO J. (2000) [Pubmed]
  12. Phosphorylation of the vasodilator-stimulated phosphoprotein regulates its interaction with actin. Harbeck, B., Hüttelmaier, S., Schluter, K., Jockusch, B.M., Illenberger, S. J. Biol. Chem. (2000) [Pubmed]
  13. The orthologous human and murine semaphorin 6A-1 proteins (SEMA6A-1/Sema6A-1) bind to the enabled/vasodilator-stimulated phosphoprotein-like protein (EVL) via a novel carboxyl-terminal zyxin-like domain. Klostermann, A., Lutz, B., Gertler, F., Behl, C. J. Biol. Chem. (2000) [Pubmed]
  14. PREL1 provides a link from Ras signalling to the actin cytoskeleton via Ena/VASP proteins. Jenzora, A., Behrendt, B., Small, J.V., Wehland, J., Stradal, T.E. FEBS Lett. (2005) [Pubmed]
  15. The proline-rich focal adhesion and microfilament protein VASP is a ligand for profilins. Reinhard, M., Giehl, K., Abel, K., Haffner, C., Jarchau, T., Hoppe, V., Jockusch, B.M., Walter, U. EMBO J. (1995) [Pubmed]
  16. Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the Arp2/3 complex link T cell receptor (TCR) signaling to the actin cytoskeleton. Krause, M., Sechi, A.S., Konradt, M., Monner, D., Gertler, F.B., Wehland, J. J. Cell Biol. (2000) [Pubmed]
  17. Ena/VASP proteins enhance actin polymerization in the presence of barbed end capping proteins. Barzik, M., Kotova, T.I., Higgs, H.N., Hazelwood, L., Hanein, D., Gertler, F.B., Schafer, D.A. J. Biol. Chem. (2005) [Pubmed]
  18. The interaction of the cell-contact proteins VASP and vinculin is regulated by phosphatidylinositol-4,5-bisphosphate. Hüttelmaier, S., Mayboroda, O., Harbeck, B., Jarchau, T., Jockusch, B.M., Rüdiger, M. Curr. Biol. (1998) [Pubmed]
  19. Modulation of lamellipodial structure and dynamics by NO-dependent phosphorylation of VASP Ser239. Lindsay, S.L., Ramsey, S., Aitchison, M., Renné, T., Evans, T.J. J. Cell. Sci. (2007) [Pubmed]
  20. Vasodilator-stimulated phosphoprotein phosphorylation analysis prior to percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events. Bonello, L., Paganelli, F., Arpin-Bornet, M., Auquier, P., Sampol, J., Dignat-George, F., Barragan, P., Camoin-Jau, L. J. Thromb. Haemost. (2007) [Pubmed]
  21. VASP interaction with vinculin: a recurring theme of interactions with proline-rich motifs. Reinhard, M., Rüdiger, M., Jockusch, B.M., Walter, U. FEBS Lett. (1996) [Pubmed]
  22. Identification, purification, and characterization of a zyxin-related protein that binds the focal adhesion and microfilament protein VASP (vasodilator-stimulated phosphoprotein). Reinhard, M., Jouvenal, K., Tripier, D., Walter, U. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  23. Profilin interacts with the Gly-Pro-Pro-Pro-Pro-Pro sequences of vasodilator-stimulated phosphoprotein (VASP): implications for actin-based Listeria motility. Kang, F., Laine, R.O., Bubb, M.R., Southwick, F.S., Purich, D.L. Biochemistry (1997) [Pubmed]
  24. A WASp-VASP complex regulates actin polymerization at the plasma membrane. Castellano, F., Le Clainche, C., Patin, D., Carlier, M.F., Chavrier, P. EMBO J. (2001) [Pubmed]
  25. The focal-adhesion vasodilator-stimulated phosphoprotein (VASP) binds to the proline-rich domain in vinculin. Brindle, N.P., Holt, M.R., Davies, J.E., Price, C.J., Critchley, D.R. Biochem. J. (1996) [Pubmed]
  26. Vasodilator-stimulated phosphoprotein (VASP) is phosphorylated on Ser157 by protein kinase C-dependent and -independent mechanisms in thrombin-stimulated human platelets. Wentworth, J.K., Pula, G., Poole, A.W. Biochem. J. (2006) [Pubmed]
  27. A comparative study of the actin-based motilities of the pathogenic bacteria Listeria monocytogenes, Shigella flexneri and Rickettsia conorii. Gouin, E., Gantelet, H., Egile, C., Lasa, I., Ohayon, H., Villiers, V., Gounon, P., Sansonetti, P.J., Cossart, P. J. Cell. Sci. (1999) [Pubmed]
  28. Vasodilator-stimulated phosphoprotein expression and its cytokine-mediated regulation in vasculogenesis during human placental development. Kayisli, U.A., Demir, R., Erguler, G., Arici, A. Mol. Hum. Reprod. (2002) [Pubmed]
  29. Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics. Krause, M., Leslie, J.D., Stewart, M., Lafuente, E.M., Valderrama, F., Jagannathan, R., Strasser, G.A., Rubinson, D.A., Liu, H., Way, M., Yaffe, M.B., Boussiotis, V.A., Gertler, F.B. Dev. Cell (2004) [Pubmed]
  30. N-WASP, WAVE and Mena play different roles in the organization of actin cytoskeleton in lamellipodia. Nakagawa, H., Miki, H., Ito, M., Ohashi, K., Takenawa, T., Miyamoto, S. J. Cell. Sci. (2001) [Pubmed]
  31. MIG-10/lamellipodin and AGE-1/PI3K promote axon guidance and outgrowth in response to slit and netrin. Chang, C., Adler, C.E., Krause, M., Clark, S.G., Gertler, F.B., Tessier-Lavigne, M., Bargmann, C.I. Curr. Biol. (2006) [Pubmed]
  32. The conformational state of Tes regulates its zyxin-dependent recruitment to focal adhesions. Garvalov, B.K., Higgins, T.E., Sutherland, J.D., Zettl, M., Scaplehorn, N., Köcher, T., Piddini, E., Griffiths, G., Way, M. J. Cell Biol. (2003) [Pubmed]
  33. LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity. Petit, M.M., Fradelizi, J., Golsteyn, R.M., Ayoubi, T.A., Menichi, B., Louvard, D., Van de Ven, W.J., Friederich, E. Mol. Biol. Cell (2000) [Pubmed]
  34. Actin-based motility of Burkholderia pseudomallei involves the Arp 2/3 complex, but not N-WASP and Ena/VASP proteins. Breitbach, K., Rottner, K., Klocke, S., Rohde, M., Jenzora, A., Wehland, J., Steinmetz, I. Cell. Microbiol. (2003) [Pubmed]
  35. Cloning of the VASP (vasodilator-stimulated phosphoprotein) genes in human and mouse: structure, sequence, and chromosomal localization. Zimmer, M., Fink, T., Fischer, L., Hauser, W., Scherer, K., Lichter, P., Walter, U. Genomics (1996) [Pubmed]
  36. Myosin X transports Mena/VASP to the tip of filopodia. Tokuo, H., Ikebe, M. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  37. Palladin is a novel binding partner for Ena/VASP family members. Boukhelifa, M., Parast, M.M., Bear, J.E., Gertler, F.B., Otey, C.A. Cell Motil. Cytoskeleton (2004) [Pubmed]
WikiGenes - Universities