Vasodilator-stimulated phosphoprotein explained

Vasodilator-stimulated phosphoprotein is a protein that in humans is encoded by the VASP gene.^{[1] [2]}

Function

Vasodilator-stimulated phosphoprotein (VASP) is a member of the Ena-VASP protein family. Ena-VASP family members contain an N-terminal EVH1 domain that binds proteins containing E/DFPPPPXD/E motifs and targets Ena-VASP proteins to focal adhesions cell membranes. In the mid-region of the protein, family members have a proline-rich region 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.

Interactions

Vasodilator-stimulated phosphoprotein has been shown to interact with Zyxin,^{[3] [4]} Profilin 1,^[3] and PFN2.^{[3] [5]}

Further reading

• Reinhard M, Halbrügge M, Scheer U, etal . 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 . 1992 . 1318192 . 10.1002/j.1460-2075.1992.tb05264.x. 556672 .
• Halbrügge M, Eigenthaler M, Polke C, Walter U . Protein phosphorylation regulated by cyclic nucleotide-dependent protein kinases in cell extracts and in intact human lymphocytes . Cell. Signal. . 4 . 2 . 189–99 . 1992 . 1319722 . 10.1016/0898-6568(92)90082-J .
• Reinhard M, Jouvenal K, Tripier D, Walter U . 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 . 1995 . 7644520 . 10.1073/pnas.92.17.7956 . 41265 . 1995PNAS...92.7956R . free .
• Reinhard M, Giehl K, Abel K, etal . The proline-rich focal adhesion and microfilament protein VASP is a ligand for profilins . EMBO J. . 14 . 8 . 1583–9 . 1995 . 7737110 . 10.1002/j.1460-2075.1995.tb07146.x. 398250 .
• Haffner C, Jarchau T, Reinhard M, etal . Molecular cloning, structural analysis and functional expression of the proline-rich focal adhesion and microfilament-associated protein VASP . EMBO J. . 14 . 1 . 19–27 . 1995 . 7828592 . 10.1002/j.1460-2075.1995.tb06971.x. 398048 .
• Horstrup K, Jablonka B, Hönig-Liedl P, etal . 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 . 1994 . 7925440 . 10.1111/j.1432-1033.1994.00021.x . free .
• Butt E, Abel K, Krieger M, etal . 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 . 1994 . 10.1016/S0021-9258(17)36652-8 . 8182057 . free .
• Laurent V, Loisel TP, Harbeck B, etal . Role of proteins of the Ena/VASP family in actin-based motility of Listeria monocytogenes . J. Cell Biol. . 144 . 6 . 1245–58 . 1999 . 10087267 . 10.1083/jcb.144.6.1245 . 2150578 .
• Bachmann C, Fischer L, Walter U, Reinhard M . The EVH2 domain of the vasodilator-stimulated phosphoprotein mediates tetramerization, F-actin binding, and actin bundle formation . J. Biol. Chem. . 274 . 33 . 23549–57 . 1999 . 10438535 . 10.1074/jbc.274.33.23549 . free .
• Petit MM, Fradelizi J, Golsteyn RM, etal . LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity . Mol. Biol. Cell . 11 . 1 . 117–29 . 2000 . 10637295 . 10.1091/mbc.11.1.117. 14761 .
• Krause M, Sechi AS, Konradt M, etal . 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 . 2000 . 10747096 . 10.1083/jcb.149.1.181 . 2175102 .
• Drees B, Friederich E, Fradelizi J, etal . Characterization of the interaction between zyxin and members of the Ena/vasodilator-stimulated phosphoprotein family of proteins . J. Biol. Chem. . 275 . 29 . 22503–11 . 2000 . 10801818 . 10.1074/jbc.M001698200 . free .
• Smolenski A, Poller W, Walter U, Lohmann SM . Regulation of human endothelial cell focal adhesion sites and migration by cGMP-dependent protein kinase I . J. Biol. Chem. . 275 . 33 . 25723–32 . 2000 . 10851246 . 10.1074/jbc.M909632199 . free .
• Harbeck B, Hüttelmaier S, Schluter K, etal . Phosphorylation of the vasodilator-stimulated phosphoprotein regulates its interaction with actin . J. Biol. Chem. . 275 . 40 . 30817–25 . 2000 . 10882740 . 10.1074/jbc.M005066200 . free .
• Burkhardt M, Glazova M, Gambaryan S, etal . 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 . 2000 . 10922374 . 10.1074/jbc.M005670200 . free .
• Ball LJ, Kühne R, Hoffmann B, etal . Dual epitope recognition by the VASP EVH1 domain modulates polyproline ligand specificity and binding affinity . EMBO J. . 19 . 18 . 4903–14 . 2000 . 10990454 . 10.1093/emboj/19.18.4903 . 314220 .
• Bearer EL, Prakash JM, Manchester RD, Allen PG . VASP protects actin filaments from gelsolin: an in vitro study with implications for platelet actin reorganizations . Cell Motil. Cytoskeleton . 47 . 4 . 351–64 . 2001 . 11093254 . 10.1002/1097-0169(200012)47:4<351::AID-CM8>3.0.CO;2-8 . 3376085.
• Lawrence DW, Pryzwansky KB . The vasodilator-stimulated phosphoprotein is regulated by cyclic GMP-dependent protein kinase during neutrophil spreading . J. Immunol. . 166 . 9 . 5550–6 . 2001 . 11313394 . 10.4049/jimmunol.166.9.5550. free .
• Castellano F, Le Clainche C, Patin D, etal . A WASp-VASP complex regulates actin polymerization at the plasma membrane . EMBO J. . 20 . 20 . 5603–14 . 2001 . 11598004 . 10.1093/emboj/20.20.5603 . 125672 .

Notes and References

1. 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 . 2 . 227–33 . January 1997 . 8812448 . 10.1006/geno.1996.0457 .
2. Web site: Entrez Gene: VASP vasodilator-stimulated phosphoprotein.
3. Harbeck . B . Hüttelmaier S . Schluter K . Jockusch B M . Illenberger S . October 2000 . Phosphorylation of the vasodilator-stimulated phosphoprotein regulates its interaction with actin . J. Biol. Chem. . 275 . 40 . 30817–25 . 0021-9258. 10882740 . 10.1074/jbc.M005066200 . free .
4. Drees . B . Friederich E . Fradelizi J . Louvard D . Beckerle M C . Golsteyn R M . July 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 . 0021-9258. 10801818 . 10.1074/jbc.M001698200 . free .
5. Reinhard . M . Giehl K . Abel K . Haffner C . Jarchau T . Hoppe V . Jockusch B M . Walter U . April 1995 . The proline-rich focal adhesion and microfilament protein VASP is a ligand for profilins . EMBO J. . 14 . 8 . 1583–9 . 0261-4189. 7737110 . 398250 . 10.1002/j.1460-2075.1995.tb07146.x .