Vasodilator-stimulated phosphoprotein
| Vasodilator-stimulated phosphoprotein | |||||||||||
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 PDB rendering based on 1egx. | |||||||||||
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| Symbols | VASP ; | ||||||||||
| External IDs | Template:OMIM5 Template:MGI HomoloGene: 7592 | ||||||||||
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| Species | Human | Mouse | |||||||||
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Overview
Vasodilator-stimulated phosphoprotein, also known as VASP, is a human gene.[1]
Vasodilator-stimulated phosphoprotein (VASP) is a member of the Ena-VASP protein family. Ena-VASP family members contain an EHV1 N-terminal domain that binds proteins containing E/DFPPPPXD/E motifs and targets Ena-VASP proteins to focal adhesions. In the mid-region of the protein, family members have a proline-rich domain that binds SH3 and WW domain-containing proteins. Their C-terminal EVH2 domain mediates tetramerization and binds both G and F actin. VASP is associated with filamentous actin formation and likely plays a widespread role in cell adhesion and motility. VASP may also be involved in the intracellular signaling pathways that regulate integrin-extracellular matrix interactions. VASP is regulated by the cyclic nucleotide-dependent kinases PKA and PKG.[1]
VASP-P
The phosphorylation (P) of vasodilator-stimulated phosphoprotein (VASP) is a test based on flow cytometry which is very specific to the P2Y12 signaling pathway. It is commercially available as a kit marketed as PLT VASP/P2Y12 (BioCytex, Marseilles, France).
VASP is an intracellular platelet protein that is not phosphorilated at baseline. VASP-P is mediated by the cAMP cascade, which is enhanced by prostaglandin E1 (PGE1) and inhibited by the link between ADP and P2Y12 receptors. Therefore, VASP-P is a marker of P2Y12 receptor inhibition, whereas its non-phosphorylated counterpart correlates with the non-inhibited form of the P2Y12 receptor.
By using the PLT VASP/P2Y12 kit, the effect of clopidogrel can be demonstrated by the persistence of VASP in its phosphorylated state (VASP-P) induced by PGE1 despite the simultaneous addition of ADP.
More in detail, the blood sample is first incubated with PGE1 alone or PGE1 + ADP. Subsequently, after a cellular permeabilization, VASP-P is labeled by indirect no wash immunofluorescence using a specific monoclonal antibody. The two tested conditions are then evaluated by means of dual color flow cytometry analysis. Final results are usually expressed in terms of platelet reactivity index (PRI), which is calculated using corrected mean fluorescence intensities (MFIc) in the presence of PGE1 alone or PGE1 and ADP simultaneously, according to the following formula:
PRI = [(MFIcPGE1 - MFIc PGE1+ADP)/ MFIcPGE1]x100
Assessment of VASP-P requires a low sample volume and is performed on whole blood. Another advantage is the opportunity to ship blood samples at room temperature to a central core laboratory. Ultimately, it correlates well with light transmittance aggregometry and VerifyNow technologies. However, sample preparation is time consuming and the reliability of the results is highly dependent from the presence of a skilled technician. Also, a flow cytometer is required.
References
Further reading
- Reinhard M, Halbrügge M, Scheer U; et al. (1992). "The 46/50 kDa phosphoprotein VASP purified from human platelets is a novel protein associated with actin filaments and focal contacts". EMBO J. 11 (6): 2063–70. PMID 1318192.
- Halbrügge M, Eigenthaler M, Polke C, Walter U (1992). "Protein phosphorylation regulated by cyclic nucleotide-dependent protein kinases in cell extracts and in intact human lymphocytes". Cell. Signal. 4 (2): 189–99. PMID 1319722.
- Reinhard M, Jouvenal K, Tripier D, Walter U (1995). "Identification, purification, and characterization of a zyxin-related protein that binds the focal adhesion and microfilament protein VASP (vasodilator-stimulated phosphoprotein)". Proc. Natl. Acad. Sci. U.S.A. 92 (17): 7956–60. PMID 7644520.
- Reinhard M, Giehl K, Abel K; et al. (1995). "The proline-rich focal adhesion and microfilament protein VASP is a ligand for profilins". EMBO J. 14 (8): 1583–9. PMID 7737110.
- Haffner C, Jarchau T, Reinhard M; et al. (1995). "Molecular cloning, structural analysis and functional expression of the proline-rich focal adhesion and microfilament-associated protein VASP". EMBO J. 14 (1): 19–27. PMID 7828592.
- Horstrup K, Jablonka B, Hönig-Liedl P; et al. (1994). "Phosphorylation of focal adhesion vasodilator-stimulated phosphoprotein at Ser157 in intact human platelets correlates with fibrinogen receptor inhibition". Eur. J. Biochem. 225 (1): 21–7. PMID 7925440.
- Butt E, Abel K, Krieger M; et al. (1994). "cAMP- and cGMP-dependent protein kinase phosphorylation sites of the focal adhesion vasodilator-stimulated phosphoprotein (VASP) in vitro and in intact human platelets". J. Biol. Chem. 269 (20): 14509–17. PMID 8182057.
- Zimmer M, Fink T, Fischer L; et al. (1997). "Cloning of the VASP (vasodilator-stimulated phosphoprotein) genes in human and mouse: structure, sequence, and chromosomal localization". Genomics. 36 (2): 227–33. doi:10.1006/geno.1996.0457. PMID 8812448.
- Laurent V, Loisel TP, Harbeck B; et al. (1999). "Role of proteins of the Ena/VASP family in actin-based motility of Listeria monocytogenes". J. Cell Biol. 144 (6): 1245–58. PMID 10087267.
- Bachmann C, Fischer L, Walter U, Reinhard M (1999). "The EVH2 domain of the vasodilator-stimulated phosphoprotein mediates tetramerization, F-actin binding, and actin bundle formation". J. Biol. Chem. 274 (33): 23549–57. PMID 10438535.
- Petit MM, Fradelizi J, Golsteyn RM; et al. (2000). "LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity". Mol. Biol. Cell. 11 (1): 117–29. PMID 10637295.
- Krause M, Sechi AS, Konradt M; et al. (2000). "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". J. Cell Biol. 149 (1): 181–94. PMID 10747096.
- Drees B, Friederich E, Fradelizi J; et al. (2000). "Characterization of the interaction between zyxin and members of the Ena/vasodilator-stimulated phosphoprotein family of proteins". J. Biol. Chem. 275 (29): 22503–11. doi:10.1074/jbc.M001698200. PMID 10801818.
- Smolenski A, Poller W, Walter U, Lohmann SM (2000). "Regulation of human endothelial cell focal adhesion sites and migration by cGMP-dependent protein kinase I.". J. Biol. Chem. 275 (33): 25723–32. doi:10.1074/jbc.M909632199. PMID 10851246.
- Harbeck B, Hüttelmaier S, Schluter K; et al. (2000). "Phosphorylation of the vasodilator-stimulated phosphoprotein regulates its interaction with actin". J. Biol. Chem. 275 (40): 30817–25. doi:10.1074/jbc.M005066200. PMID 10882740.
- Burkhardt M, Glazova M, Gambaryan S; et al. (2000). "KT5823 inhibits cGMP-dependent protein kinase activity in vitro but not in intact human platelets and rat mesangial cells". J. Biol. Chem. 275 (43): 33536–41. doi:10.1074/jbc.M005670200. PMID 10922374.
- Ball LJ, Kühne R, Hoffmann B; et al. (2000). "Dual epitope recognition by the VASP EVH1 domain modulates polyproline ligand specificity and binding affinity". EMBO J. 19 (18): 4903–14. doi:10.1093/emboj/19.18.4903. PMID 10990454.
- Bearer EL, Prakash JM, Manchester RD, Allen PG (2001). "VASP protects actin filaments from gelsolin: an in vitro study with implications for platelet actin reorganizations". Cell Motil. Cytoskeleton. 47 (4): 351–64. doi:10.1002/1097-0169(200012)47:4<351::AID-CM8>3.0.CO;2-8. PMID 11093254.
- Lawrence DW, Pryzwansky KB (2001). "The vasodilator-stimulated phosphoprotein is regulated by cyclic GMP-dependent protein kinase during neutrophil spreading". J. Immunol. 166 (9): 5550–6. PMID 11313394.
- Castellano F, Le Clainche C, Patin D; et al. (2001). "A WASp-VASP complex regulates actin polymerization at the plasma membrane". EMBO J. 20 (20): 5603–14. doi:10.1093/emboj/20.20.5603. PMID 11598004.