From Wikipedia, the free encyclopedia
Human protein and coding gene
Proto-oncogene vav is a
protein that in humans is encoded by the VAV1
gene .
[5]
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.
[6]
Interactions
VAV1 has been shown to
interact with:
ARHGDIB ,
[7]
Abl gene ,
[8]
Cbl gene
[9]
[10]
EZH2 ,
[11]
Grb2 ,
[12]
[13]
[14]
[15]
JAK2 ,
[16]
[17]
Ku70 ,
[18]
LAT ,
[19]
[20]
LCP2 ,
[21]
[22]
MAPK1 ,
[13]
[15]
PIK3R1 ,
[16]
[23]
PLCG1 ,
[23]
PRKCQ ,
[24]
S100B ,
[25]
SHB ,
[26]
SIAH2 ,
[12] and
Syk .
[9]
[13]
[27]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000141968 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000034116 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Han J, Luby-Phelps K, Das B, Shu X, Xia Y, Mosteller RD, Krishna UM,
Falck JR , White MA, Broek D (February 1998). "Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav". Science . 279 (5350): 558–60.
Bibcode :
1998Sci...279..558H .
doi :
10.1126/science.279.5350.558 .
PMID
9438848 .
^
"Entrez Gene: VAV1 vav 1 oncogene" .
^ Groysman M, Russek CS, Katzav S (February 2000).
"Vav, a GDP/GTP nucleotide exchange factor, interacts with GDIs, proteins that inhibit GDP/GTP dissociation" . FEBS Lett . 467 (1): 75–80.
doi :
10.1016/S0014-5793(00)01121-2 .
PMID
10664460 .
S2CID
40103095 .
^ Bassermann F, Jahn T, Miething C, Seipel P, Bai RY, Coutinho S, Tybulewicz VL, Peschel C, Duyster J (April 2002).
"Association of Bcr-Abl with the proto-oncogene Vav is implicated in activation of the Rac-1 pathway" . J. Biol. Chem . 277 (14): 12437–45.
doi :
10.1074/jbc.M112397200 .
PMID
11790798 .
^
a
b Bertagnolo V, Marchisio M, Brugnoli F, Bavelloni A, Boccafogli L, Colamussi ML, Capitani S (April 2001). "Requirement of tyrosine-phosphorylated Vav for morphological differentiation of all-trans-retinoic acid-treated HL-60 cells". Cell Growth Differ . 12 (4): 193–200.
PMID
11331248 .
^ Marengère LE, Mirtsos C, Kozieradzki I, Veillette A, Mak TW, Penninger JM (July 1997).
"Proto-oncoprotein Vav interacts with c-Cbl in activated thymocytes and peripheral T cells" . J. Immunol . 159 (1): 70–6.
doi :
10.4049/jimmunol.159.1.70 .
PMID
9200440 .
^ Hobert O, Jallal B, Ullrich A (June 1996).
"Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression" . Mol. Cell. Biol . 16 (6): 3066–73.
doi :
10.1128/MCB.16.6.3066 .
PMC
231301 .
PMID
8649418 .
^
a
b Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S, Varin-Blank N (May 1999).
"hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways" . Mol. Cell. Biol . 19 (5): 3798–807.
doi :
10.1128/MCB.19.5.3798 .
PMC
84217 .
PMID
10207103 .
^
a
b
c Song JS, Gomez J, Stancato LF, Rivera J (October 1996).
"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" . J. Biol. Chem . 271 (43): 26962–70.
doi :
10.1074/jbc.271.43.26962 .
PMID
8900182 .
^ Ye ZS, Baltimore D (Dec 1994).
"Binding of Vav to Grb2 through dimerization of Src homology 3 domains" . Proc. Natl. Acad. Sci. U.S.A . 91 (26): 12629–33.
Bibcode :
1994PNAS...9112629Y .
doi :
10.1073/pnas.91.26.12629 .
PMC
45492 .
PMID
7809090 .
^
a
b Lee IS, Liu Y, Narazaki M, Hibi M, Kishimoto T, Taga T (January 1997).
"Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6" . FEBS Lett . 401 (2–3): 133–7.
doi :
10.1016/s0014-5793(96)01456-1 .
PMID
9013873 .
S2CID
32632406 .
^
a
b Shigematsu H, Iwasaki H, Otsuka T, Ohno Y, Arima F, Niho Y (May 1997).
"Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell proliferation and phosphatidylinositol 3-kinase activity" . J. Biol. Chem . 272 (22): 14334–40.
doi :
10.1074/jbc.272.22.14334 .
PMID
9162069 .
^ Matsuguchi T, Inhorn RC, Carlesso N, Xu G, Druker B, Griffin JD (January 1995).
"Tyrosine phosphorylation of p95Vav in myeloid cells is regulated by GM-CSF, IL-3 and steel factor and is constitutively increased by p210BCR/ABL" . EMBO J . 14 (2): 257–65.
doi :
10.1002/j.1460-2075.1995.tb06999.x .
PMC
398079 .
PMID
7530656 .
^ Romero F, Dargemont C, Pozo F, Reeves WH, Camonis J, Gisselbrecht S, Fischer S (January 1996).
"p95vav associates with the nuclear protein Ku-70" . Mol. Cell. Biol . 16 (1): 37–44.
doi :
10.1128/mcb.16.1.37 .
PMC
230976 .
PMID
8524317 .
^ Paz PE, Wang S, Clarke H, Lu X, Stokoe D, Abo A (June 2001).
"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" . Biochem. J . 356 (Pt 2): 461–71.
doi :
10.1042/0264-6021:3560461 .
PMC
1221857 .
PMID
11368773 .
^ Perez-Villar JJ, Whitney GS, Sitnick MT, Dunn RJ, Venkatesan S, O'Day K, Schieven GL, Lin TA, Kanner SB (August 2002). "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry . 41 (34): 10732–40.
doi :
10.1021/bi025554o .
PMID
12186560 .
^ Raab M, da Silva AJ, Findell PR, Rudd CE (February 1997).
"Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2" . Immunity . 6 (2): 155–64.
doi :
10.1016/s1074-7613(00)80422-7 .
PMID
9047237 .
^ Onodera H, Motto DG, Koretzky GA, Rothstein DM (September 1996).
"Differential regulation of activation-induced tyrosine phosphorylation and recruitment of SLP-76 to Vav by distinct isoforms of the CD45 protein-tyrosine phosphatase" . J. Biol. Chem . 271 (36): 22225–30.
doi :
10.1074/jbc.271.36.22225 .
PMID
8703037 .
^
a
b Bertagnolo V, Marchisio M, Volinia S, Caramelli E, Capitani S (Dec 1998).
"Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells" . FEBS Lett . 441 (3): 480–4.
doi :
10.1016/s0014-5793(98)01593-2 .
PMID
9891995 .
S2CID
38371954 .
^ Hehner SP, Li-Weber M, Giaisi M, Dröge W, Krammer PH, Schmitz ML (April 2000).
"Vav synergizes with protein kinase C theta to mediate IL-4 gene expression in response to CD28 costimulation in T cells" . J. Immunol . 164 (7): 3829–36.
doi :
10.4049/jimmunol.164.7.3829 .
PMID
10725744 .
^ Fackler OT, Luo W, Geyer M, Alberts AS, Peterlin BM (June 1999).
"Activation of Vav by Nef induces cytoskeletal rearrangements and downstream effector functions" . Mol. Cell . 3 (6): 729–39.
doi :
10.1016/S1097-2765(01)80005-8 .
PMID
10394361 .
^ Lindholm CK, Henriksson ML, Hallberg B, Welsh M (July 2002). "Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells". Eur. J. Biochem . 269 (13): 3279–88.
doi :
10.1046/j.1432-1033.2002.03008.x .
PMID
12084069 .
^ Deckert M, Tartare-Deckert S, Couture C, Mustelin T, Altman A (Dec 1996).
"Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product" . Immunity . 5 (6): 591–604.
doi :
10.1016/s1074-7613(00)80273-3 .
PMID
8986718 .
Further reading
Romero F, Fischer S (1997). "Structure and function of vav". Cell. Signal . 8 (8): 545–53.
doi :
10.1016/S0898-6568(96)00118-0 .
PMID
9115846 .
Bustelo XR (2000).
"Regulatory and Signaling Properties of the Vav Family" . Mol. Cell. Biol . 20 (5): 1461–77.
doi :
10.1128/MCB.20.5.1461-1477.2000 .
PMC
85310 .
PMID
10669724 .
Geyer M, Fackler OT, Peterlin BM (2001).
"Structure–function relationships in HIV-1 Nef" . EMBO Rep . 2 (7): 580–5.
doi :
10.1093/embo-reports/kve141 .
PMC
1083955 .
PMID
11463741 .
Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (2004). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication". J. Biosci . 28 (3): 323–35.
doi :
10.1007/BF02970151 .
PMID
12734410 .
S2CID
33749514 .
Anderson JL, Hope TJ (2005). "HIV accessory proteins and surviving the host cell". Current HIV/AIDS Reports . 1 (1): 47–53.
doi :
10.1007/s11904-004-0007-x .
PMID
16091223 .
S2CID
34731265 .
Stove V, Verhasselt B (2006). "Modelling thymic HIV-1 Nef effects". Curr. HIV Res . 4 (1): 57–64.
doi :
10.2174/157016206775197583 .
PMID
16454711 .
Katzav S (2007). "Flesh and blood: the story of Vav1, a gene that signals in hematopoietic cells but can be transforming in human malignancies". Cancer Lett . 255 (2): 241–54.
doi :
10.1016/j.canlet.2007.04.015 .
PMID
17590270 .
Bustelo XR, Barbacid M (1992). "Tyrosine phosphorylation of the vav proto-oncogene product in activated B cells". Science . 256 (5060): 1196–9.
Bibcode :
1992Sci...256.1196B .
doi :
10.1126/science.256.5060.1196 .
PMID
1375396 .
S2CID
35071104 .
Adams JM, Houston H, Allen J, Lints T, Harvey R (1992). "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". Oncogene . 7 (4): 611–8.
PMID
1565462 .
Katzav S, Cleveland JL, Heslop HE, Pulido D (1991).
"Loss of the amino-terminal helix-loop-helix domain of the vav proto-oncogene activates its transforming potential" . Mol. Cell. Biol . 11 (4): 1912–20.
doi :
10.1128/MCB.11.4.1912 .
PMC
359873 .
PMID
2005887 .
Coppola J, Bryant S, Koda T, Conway D, Barbacid M (1991). "Mechanism of activation of the vav protooncogene". Cell Growth Differ . 2 (2): 95–105.
PMID
2069873 .
Katzav S, Martin-Zanca D, Barbacid M (1989).
"vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoietic cells" . EMBO J . 8 (8): 2283–90.
doi :
10.1002/j.1460-2075.1989.tb08354.x .
PMC
401160 .
PMID
2477241 .
Ramos-Morales F, Romero F, Schweighoffer F, Bismuth G, Camonis J, Tortolero M, Fischer S (1995). "The proline-rich region of Vav binds to Grb2 and Grb3-3". Oncogene . 11 (8): 1665–9.
PMID
7478592 .
Weng WK, Jarvis L, LeBien TW (1995).
"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" . J. Biol. Chem . 269 (51): 32514–21.
doi :
10.1016/S0021-9258(18)31664-8 .
PMID
7528218 .
Matsuguchi T, Inhorn RC, Carlesso N, Xu G, Druker B, Griffin JD (1995).
"Tyrosine phosphorylation of p95Vav in myeloid cells is regulated by GM-CSF, IL-3 and steel factor and is constitutively increased by p210BCR/ABL" . EMBO J . 14 (2): 257–65.
doi :
10.1002/j.1460-2075.1995.tb06999.x .
PMC
398079 .
PMID
7530656 .
Uddin S, Katzav S, White MF, Platanias LC (1995).
"Insulin-dependent tyrosine phosphorylation of the vav protooncogene product in cells of hematopoietic origin" . J. Biol. Chem . 270 (13): 7712–6.
doi :
10.1074/jbc.270.13.7712 .
PMID
7535775 .
Machide M, Mano H, Todokoro K (1995). "Interleukin 3 and erythropoietin induce association of Vav with Tec kinase through Tec homology domain". Oncogene . 11 (4): 619–25.
PMID
7651724 .
Clevenger CV, Ngo W, Sokol DL, Luger SM, Gewirtz AM (1995).
"Vav is necessary for prolactin-stimulated proliferation and is translocated into the nucleus of a T-cell line" . J. Biol. Chem . 270 (22): 13246–53.
doi :
10.1074/jbc.270.22.13246 .
PMID
7768923 .
Katzav S, Sutherland M, Packham G, Yi T, Weiss A (1995).
"The protein tyrosine kinase ZAP-70 can associate with the SH2 domain of proto-Vav" . J. Biol. Chem . 269 (51): 32579–85.
doi :
10.1016/S0021-9258(18)31673-9 .
PMID
7798261 .
Ye ZS, Baltimore D (1995).
"Binding of Vav to Grb2 through dimerization of Src homology 3 domains" . Proc. Natl. Acad. Sci. U.S.A . 91 (26): 12629–33.
Bibcode :
1994PNAS...9112629Y .
doi :
10.1073/pnas.91.26.12629 .
PMC
45492 .
PMID
7809090 .