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词条 VAV1
释义

  1. Function

  2. Interactions

  3. References

  4. Further reading

{{Infobox_gene}}Proto-oncogene vav is a protein that in humans is encoded by the VAV1 gene.[1]

Function

The protein encoded by this proto-oncogene is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. The protein is important in hematopoiesis, playing a role in T-cell and B-cell development and activation. This particular GEF has been identified as the specific binding partner of Nef proteins from HIV-1. Coexpression and binding of these partners initiates profound morphological changes, cytoskeletal rearrangements and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication.[2]

Interactions

VAV1 has been shown to interact with:

{{div col|colwidth=20em}}
  • ARHGDIB,[3]
  • Abl gene,[4]
  • Cbl gene[5][5]
  • EZH2,[6]
  • Grb2,[8][7][8][9]
  • JAK2,[10][11]
  • Ku70,[12]
  • LAT,[13][14]
  • LCP2,[15][16]
  • MAPK1,[7][9]
  • PIK3R1,[10][22]
  • PLCG1,[17]
  • PRKCQ,[18]
  • S100B,[19]
  • SHB,[20]
  • SIAH2,[21] and
  • Syk.[22][7][23]
{{Div col end}}

References

1. ^{{cite journal | vauthors = Han J, Luby-Phelps K, Das B, Shu X, Xia Y, Mosteller RD, Krishna UM, Falck JR, White MA, Broek D | title = Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav | journal = Science | volume = 279 | issue = 5350 | pages = 558–60 | date = February 1998 | pmid = 9438848 | pmc = | doi = 10.1126/science.279.5350.558 }}
2. ^{{cite web | title = Entrez Gene: VAV1 vav 1 oncogene| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7409| accessdate = }}
3. ^{{cite journal | vauthors = Groysman M, Russek CS, Katzav S | title = Vav, a GDP/GTP nucleotide exchange factor, interacts with GDIs, proteins that inhibit GDP/GTP dissociation | journal = FEBS Lett. | volume = 467 | issue = 1 | pages = 75–80 | date = February 2000 | pmid = 10664460 | doi = 10.1016/S0014-5793(00)01121-2 }}
4. ^{{cite journal | vauthors = Bassermann F, Jahn T, Miething C, Seipel P, Bai RY, Coutinho S, Tybulewicz VL, Peschel C, Duyster J | title = Association of Bcr-Abl with the proto-oncogene Vav is implicated in activation of the Rac-1 pathway | journal = J. Biol. Chem. | volume = 277 | issue = 14 | pages = 12437–45 | date = April 2002 | pmid = 11790798 | doi = 10.1074/jbc.M112397200 }}
5. ^{{cite journal | vauthors = Marengère LE, Mirtsos C, Kozieradzki I, Veillette A, Mak TW, Penninger JM | title = Proto-oncoprotein Vav interacts with c-Cbl in activated thymocytes and peripheral T cells | journal = J. Immunol. | volume = 159 | issue = 1 | pages = 70–6 | date = July 1997 | pmid = 9200440 | doi = }}
6. ^{{cite journal | vauthors = Hobert O, Jallal B, Ullrich A | title = Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression | journal = Mol. Cell. Biol. | volume = 16 | issue = 6 | pages = 3066–73 | date = June 1996 | pmid = 8649418 | pmc = 231301 | doi = 10.1128/MCB.16.6.3066}}
7. ^1 2 {{cite journal | vauthors = Song JS, Gomez J, Stancato LF, Rivera J | title = Association of a p95 Vav-containing signaling complex with the FcepsilonRI gamma chain in the RBL-2H3 mast cell line. Evidence for a constitutive in vivo association of Vav with Grb2, Raf-1, and ERK2 in an active complex | journal = J. Biol. Chem. | volume = 271 | issue = 43 | pages = 26962–70 | date = October 1996 | pmid = 8900182 | doi = 10.1074/jbc.271.43.26962 }}
8. ^{{cite journal | vauthors = Ye ZS, Baltimore D | title = Binding of Vav to Grb2 through dimerization of Src homology 3 domains | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 91 | issue = 26 | pages = 12629–33 | date = Dec 1994 | pmid = 7809090 | pmc = 45492 | doi = 10.1073/pnas.91.26.12629 }}
9. ^1 {{cite journal | vauthors = Lee IS, Liu Y, Narazaki M, Hibi M, Kishimoto T, Taga T | title = Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6 | journal = FEBS Lett. | volume = 401 | issue = 2–3 | pages = 133–7 | date = January 1997 | pmid = 9013873 | doi = 10.1016/s0014-5793(96)01456-1 }}
10. ^1 {{cite journal | vauthors = Shigematsu H, Iwasaki H, Otsuka T, Ohno Y, Arima F, Niho Y | title = Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity | journal = J. Biol. Chem. | volume = 272 | issue = 22 | pages = 14334–40 | date = May 1997 | pmid = 9162069 | doi = 10.1074/jbc.272.22.14334 }}
11. ^{{cite journal | vauthors = Matsuguchi T, Inhorn RC, Carlesso N, Xu G, Druker B, Griffin JD | title = Tyrosine phosphorylation of p95Vav in myeloid cells is regulated by GM-CSF, IL-3 and steel factor and is constitutively increased by p210BCR/ABL | journal = EMBO J. | volume = 14 | issue = 2 | pages = 257–65 | date = January 1995 | pmid = 7530656 | pmc = 398079 | doi = 10.1002/j.1460-2075.1995.tb06999.x}}
12. ^{{cite journal | vauthors = Romero F, Dargemont C, Pozo F, Reeves WH, Camonis J, Gisselbrecht S, Fischer S | title = p95vav associates with the nuclear protein Ku-70 | journal = Mol. Cell. Biol. | volume = 16 | issue = 1 | pages = 37–44 | date = January 1996 | pmid = 8524317 | pmc = 230976 | doi = 10.1128/mcb.16.1.37}}
13. ^{{cite journal | vauthors = Paz PE, Wang S, Clarke H, Lu X, Stokoe D, Abo A | title = Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells | journal = Biochem. J. | volume = 356 | issue = Pt 2 | pages = 461–71 | date = June 2001 | pmid = 11368773 | pmc = 1221857 | doi = 10.1042/0264-6021:3560461 }}
14. ^{{cite journal | vauthors = Perez-Villar JJ, Whitney GS, Sitnick MT, Dunn RJ, Venkatesan S, O'Day K, Schieven GL, Lin TA, Kanner SB | title = Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav | journal = Biochemistry | volume = 41 | issue = 34 | pages = 10732–40 | date = August 2002 | pmid = 12186560 | doi = 10.1021/bi025554o }}
15. ^{{cite journal | vauthors = Raab M, da Silva AJ, Findell PR, Rudd CE | title = Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2 | journal = Immunity | volume = 6 | issue = 2 | pages = 155–64 | date = February 1997 | pmid = 9047237 | doi = 10.1016/s1074-7613(00)80422-7 }}
16. ^{{cite journal | vauthors = Onodera H, Motto DG, Koretzky GA, Rothstein DM | title = Differential regulation of activation-induced tyrosine phosphorylation and recruitment of SLP-76 to Vav by distinct isoforms of the CD45 protein-tyrosine phosphatase | journal = J. Biol. Chem. | volume = 271 | issue = 36 | pages = 22225–30 | date = September 1996 | pmid = 8703037 | doi = 10.1074/jbc.271.36.22225 }}
17. ^1 {{cite journal | vauthors = Bertagnolo V, Marchisio M, Volinia S, Caramelli E, Capitani S | title = Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells | journal = FEBS Lett. | volume = 441 | issue = 3 | pages = 480–4 | date = Dec 1998 | pmid = 9891995 | doi = 10.1016/s0014-5793(98)01593-2 }}
18. ^{{cite journal | vauthors = Hehner SP, Li-Weber M, Giaisi M, Dröge W, Krammer PH, Schmitz ML | title = Vav synergizes with protein kinase C theta to mediate IL-4 gene expression in response to CD28 costimulation in T cells | journal = J. Immunol. | volume = 164 | issue = 7 | pages = 3829–36 | date = April 2000 | pmid = 10725744 | doi = 10.4049/jimmunol.164.7.3829 }}
19. ^{{cite journal | vauthors = Fackler OT, Luo W, Geyer M, Alberts AS, Peterlin BM | title = Activation of Vav by Nef induces cytoskeletal rearrangements and downstream effector functions | journal = Mol. Cell | volume = 3 | issue = 6 | pages = 729–39 | date = June 1999 | pmid = 10394361 | doi = 10.1016/S1097-2765(01)80005-8 }}
20. ^{{cite journal | vauthors = Lindholm CK, Henriksson ML, Hallberg B, Welsh M | title = Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells | journal = Eur. J. Biochem. | volume = 269 | issue = 13 | pages = 3279–88 | date = July 2002 | pmid = 12084069 | doi = 10.1046/j.1432-1033.2002.03008.x }}
21. ^1 {{cite journal | vauthors = Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S, Varin-Blank N | title = hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways | journal = Mol. Cell. Biol. | volume = 19 | issue = 5 | pages = 3798–807 | date = May 1999 | pmid = 10207103 | pmc = 84217 | doi = 10.1128/MCB.19.5.3798}}
22. ^1 {{cite journal | vauthors = Bertagnolo V, Marchisio M, Brugnoli F, Bavelloni A, Boccafogli L, Colamussi ML, Capitani S | title = Requirement of tyrosine-phosphorylated Vav for morphological differentiation of all-trans-retinoic acid-treated HL-60 cells | journal = Cell Growth Differ. | volume = 12 | issue = 4 | pages = 193–200 | date = April 2001 | pmid = 11331248 | doi = }}
23. ^{{cite journal | vauthors = Deckert M, Tartare-Deckert S, Couture C, Mustelin T, Altman A | title = Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product | journal = Immunity | volume = 5 | issue = 6 | pages = 591–604 | date = Dec 1996 | pmid = 8986718 | doi = 10.1016/s1074-7613(00)80273-3 }}

Further reading

{{Refbegin | 2}}
  • {{cite journal | vauthors = Romero F, Fischer S | title = Structure and function of vav | journal = Cell. Signal. | volume = 8 | issue = 8 | pages = 545–53 | year = 1997 | pmid = 9115846 | doi = 10.1016/S0898-6568(96)00118-0 }}
  • {{cite journal | vauthors = Bustelo XR | title = Regulatory and Signaling Properties of the Vav Family | journal = Mol. Cell. Biol. | volume = 20 | issue = 5 | pages = 1461–77 | year = 2000 | pmid = 10669724 | pmc = 85310 | doi = 10.1128/MCB.20.5.1461-1477.2000 }}
  • {{cite journal | vauthors = Geyer M, Fackler OT, Peterlin BM | title = Structure–function relationships in HIV-1 Nef | journal = EMBO Rep. | volume = 2 | issue = 7 | pages = 580–5 | year = 2001 | pmid = 11463741 | pmc = 1083955 | doi = 10.1093/embo-reports/kve141 }}
  • {{cite journal | vauthors = Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M | title = HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication | journal = J. Biosci. | volume = 28 | issue = 3 | pages = 323–35 | year = 2004 | pmid = 12734410 | doi = 10.1007/BF02970151 }}
  • {{cite journal | vauthors = Anderson JL, Hope TJ | title = HIV accessory proteins and surviving the host cell | journal = Current HIV/AIDS Reports | volume = 1 | issue = 1 | pages = 47–53 | year = 2005 | pmid = 16091223 | doi = 10.1007/s11904-004-0007-x }}
  • {{cite journal | vauthors = Stove V, Verhasselt B | title = Modelling thymic HIV-1 Nef effects | journal = Curr. HIV Res. | volume = 4 | issue = 1 | pages = 57–64 | year = 2006 | pmid = 16454711 | doi = 10.2174/157016206775197583 }}
  • {{cite journal | vauthors = Katzav S | title = Flesh and blood: the story of Vav1, a gene that signals in hematopoietic cells but can be transforming in human malignancies | journal = Cancer Lett. | volume = 255 | issue = 2 | pages = 241–54 | year = 2007 | pmid = 17590270 | doi = 10.1016/j.canlet.2007.04.015 }}
  • {{cite journal | vauthors = Bustelo XR, Barbacid M | title = Tyrosine phosphorylation of the vav proto-oncogene product in activated B cells | journal = Science | volume = 256 | issue = 5060 | pages = 1196–9 | year = 1992 | pmid = 1375396 | doi = 10.1126/science.256.5060.1196 }}
  • {{cite journal | vauthors = Adams JM, Houston H, Allen J, Lints T, Harvey R | title = The hematopoietically expressed vav proto-oncogene shares homology with the dbl GDP-GTP exchange factor, the bcr gene and a yeast gene (CDC24) involved in cytoskeletal organization | journal = Oncogene | volume = 7 | issue = 4 | pages = 611–8 | year = 1992 | pmid = 1565462 | doi = }}
  • {{cite journal | vauthors = Katzav S, Cleveland JL, Heslop HE, Pulido D | title = Loss of the amino-terminal helix-loop-helix domain of the vav proto-oncogene activates its transforming potential | journal = Mol. Cell. Biol. | volume = 11 | issue = 4 | pages = 1912–20 | year = 1991 | pmid = 2005887 | pmc = 359873 | doi = 10.1128/MCB.11.4.1912}}
  • {{cite journal | vauthors = Coppola J, Bryant S, Koda T, Conway D, Barbacid M | title = Mechanism of activation of the vav protooncogene | journal = Cell Growth Differ. | volume = 2 | issue = 2 | pages = 95–105 | year = 1991 | pmid = 2069873 | doi = }}
  • {{cite journal | vauthors = Katzav S, Martin-Zanca D, Barbacid M | title = vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoietic cells | journal = EMBO J. | volume = 8 | issue = 8 | pages = 2283–90 | year = 1989 | pmid = 2477241 | pmc = 401160 | doi = 10.1002/j.1460-2075.1989.tb08354.x}}
  • {{cite journal | vauthors = Ramos-Morales F, Romero F, Schweighoffer F, Bismuth G, Camonis J, Tortolero M, Fischer S | title = The proline-rich region of Vav binds to Grb2 and Grb3-3 | journal = Oncogene | volume = 11 | issue = 8 | pages = 1665–9 | year = 1995 | pmid = 7478592 | doi = }}
  • {{cite journal | vauthors = Weng WK, Jarvis L, LeBien TW | title = Signaling through CD19 activates Vav/mitogen-activated protein kinase pathway and induces formation of a CD19/Vav/phosphatidylinositol 3-kinase complex in human B cell precursors | journal = J. Biol. Chem. | volume = 269 | issue = 51 | pages = 32514–21 | year = 1995 | pmid = 7528218 | doi = }}
  • {{cite journal | vauthors = Matsuguchi T, Inhorn RC, Carlesso N, Xu G, Druker B, Griffin JD | title = Tyrosine phosphorylation of p95Vav in myeloid cells is regulated by GM-CSF, IL-3 and steel factor and is constitutively increased by p210BCR/ABL | journal = EMBO J. | volume = 14 | issue = 2 | pages = 257–65 | year = 1995 | pmid = 7530656 | pmc = 398079 | doi = 10.1002/j.1460-2075.1995.tb06999.x}}
  • {{cite journal | vauthors = Uddin S, Katzav S, White MF, Platanias LC | title = Insulin-dependent tyrosine phosphorylation of the vav protooncogene product in cells of hematopoietic origin | journal = J. Biol. Chem. | volume = 270 | issue = 13 | pages = 7712–6 | year = 1995 | pmid = 7535775 | doi = 10.1074/jbc.270.13.7712 }}
  • {{cite journal | vauthors = Machide M, Mano H, Todokoro K | title = Interleukin 3 and erythropoietin induce association of Vav with Tec kinase through Tec homology domain | journal = Oncogene | volume = 11 | issue = 4 | pages = 619–25 | year = 1995 | pmid = 7651724 | doi = }}
  • {{cite journal | vauthors = Clevenger CV, Ngo W, Sokol DL, Luger SM, Gewirtz AM | title = Vav is necessary for prolactin-stimulated proliferation and is translocated into the nucleus of a T-cell line | journal = J. Biol. Chem. | volume = 270 | issue = 22 | pages = 13246–53 | year = 1995 | pmid = 7768923 | doi = 10.1074/jbc.270.22.13246 }}
  • {{cite journal | vauthors = Katzav S, Sutherland M, Packham G, Yi T, Weiss A | title = The protein tyrosine kinase ZAP-70 can associate with the SH2 domain of proto-Vav | journal = J. Biol. Chem. | volume = 269 | issue = 51 | pages = 32579–85 | year = 1995 | pmid = 7798261 | doi = }}
  • {{cite journal | vauthors = Ye ZS, Baltimore D | title = Binding of Vav to Grb2 through dimerization of Src homology 3 domains | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 91 | issue = 26 | pages = 12629–33 | year = 1995 | pmid = 7809090 | pmc = 45492 | doi = 10.1073/pnas.91.26.12629 }}
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