HGNC Approved Gene Symbol: VASP
Cytogenetic location: 19q13.32 Genomic coordinates (GRCh38): 19:45,507,479-45,526,983 (from NCBI)
Human platelet activation is inhibited by agents such as prostaglandins and NO donors, which elevate cAMP or cGMP levels. The vasodilator-stimulated phosphoprotein (VASP) is phosphorylated in human platelets in response to both cAMP- and cGMP-elevating agents, and its phosphorylation correlates with platelet inhibition (summary by Haffner et al., 1995).
Haffner et al. (1995) cloned the VASP gene from human and canine cells and showed that VASP is a 380-amino acid protein with a predicted molecular mass of 39.8 kD.
Zimmer et al. (1996) cloned human and mouse VASP from genomic cosmid libraries. They determined that the human and mouse VASP genes are 89% identical at the amino acid level.
Brindle et al. (1996) showed that VASP binds to the proline-rich domain of vinculin (193065). They suggested that this interaction is important for actin-filament assembly and focal adhesion stability.
The motility of Listeria monocytogenes depends on actin polymerization. Using motility assays of Listeria in human platelet and mouse brain extracts, Laurent et al. (1999) showed that ENA (ENAH; 609061), VASP, and EVL (616912) played interchangeable roles in the transformation of actin polymerization into active movement and propulsive force. The ENA/VASP homology-1 (EVH1) domain of human VASP was in slow association-dissociation equilibrium high-affinity binding to the zyxin (ZYX; 602002)-homologous proline-rich region of ACTA (102610). VASP also interacted with F-actin via its C-terminal EVH2 domain in a ser157 phosphorylation-dependent manner. Laurent et al. (1999) concluded that VASP, EVL, and ENA link the bacterium to the actin tail to enable movement in a molecular ratchet model.
Kanchanawong et al. (2010) used 3-dimensional super-resolution fluorescence microscopy to map nanoscale protein organization in focal adhesions. Their results revealed that integrins and actin are vertically separated by an approximately 40-nm focal adhesion core region consisting of multiple protein-specific strata: a membrane-apposed integrin signaling layer containing integrin cytoplasmic tails (see 193210), focal adhesion kinase (600758), and paxillin (602505); an intermediate force-transduction layer containing talin (186745) and vinculin; and an uppermost actin-regulatory layer containing zyxin, VASP, and alpha-actinin (102575). By localizing amino- and carboxy-terminally tagged talins, Kanchanawong et al. (2010) revealed talin's polarized orientation, indicative of a role in organizing the focal adhesion strata. Kanchanawong et al. (2010) concluded that their composite multilaminar protein architecture provided a molecular blueprint for understanding focal adhesion functions.
Zimmer et al. (1996) determined that human and mouse VASP consist of 13 exons and span a genomic DNA region of approximately 20 kb.
Zimmer et al. (1996) mapped human VASP to chromosome 19q13.2-q13.3 using fluorescence in situ hybridization. They noted that VASP is located about 92 kb distal to ERCC1 (126380) and about 300 kb proximal to the myotonic dystrophy protein kinase gene (160900).
Brindle, N. P. J., Holt, M. R., Davies, J. E., Price, C. J., Critchley, D. R. The focal-adhesion vasodilator-stimulated phosphoprotein (VASP) binds to the proline-rich domain in vinculin. Biochem. J. 318: 753-757, 1996. [PubMed: 8836115] [Full Text: https://doi.org/10.1042/bj3180753]
Haffner, C., Jarchau, T., Reinhard, M., Hoppe, J., Lohmann, S. M., Walter, V. Molecular cloning, structural analysis and functional expression of the proline-rich focal adhesion and microfilament-associated protein VASP. EMBO J. 14: 19-27, 1995. [PubMed: 7828592] [Full Text: https://doi.org/10.1002/j.1460-2075.1995.tb06971.x]
Kanchanawong, P., Shtengel, G., Pasapera, A. M., Ramko, E. B., Davidson, M. W., Hess, H. F., Waterman, C. M. Nanoscale architecture of integrin-based cell adhesions. Nature 468: 580-584, 2010. [PubMed: 21107430] [Full Text: https://doi.org/10.1038/nature09621]
Laurent, V., Loisel, T. P., Harbeck, B., Wehman, A., Grobe, L., Jockusch, B. M., Wehland, J., Gertler, F. B., Carlier, M.-F. Role of proteins of the Ena/VASP family in actin-based motility of Listeria monocytogenes. J. Cell Biol. 144: 1245-1258, 1999. [PubMed: 10087267] [Full Text: https://doi.org/10.1083/jcb.144.6.1245]
Zimmer, M., Fink, T., Fischer, L., Hauser, W., Scherer, K., Lichter, P., Walter, U. Cloning of the VASP (vasodilator-stimulated phosphoprotein) genes in human and mouse: structure, sequence, and chromosomal localization. Genomics 36: 227-233, 1996. [PubMed: 8812448] [Full Text: https://doi.org/10.1006/geno.1996.0457]