VAV1

Vav 1 guanine nucleotide exchange factor

PDB rendering based on 1k1z.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsVAV1 ; VAV
External IDsOMIM: 164875 MGI: 98923 HomoloGene: 3961 GeneCards: VAV1 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez740922324
EnsemblENSG00000141968ENSMUSG00000034116
UniProtP15498P27870
RefSeq (mRNA)NM_001258206NM_001163815
RefSeq (protein)NP_001245135NP_001157287
Location (UCSC)Chr 19:
6.77 – 6.86 Mb		Chr 17:
57.28 – 57.33 Mb
PubMed search

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:

References

  1. ↑ Han J, Luby-Phelps K, Das B, Shu X, Xia Y, Mosteller RD et al. (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. doi:10.1126/science.279.5350.558. PMID 9438848.
  2. ↑ "Entrez Gene: VAV1 vav 1 oncogene".
  3. ↑ 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.
  4. ↑ Bassermann F, Jahn T, Miething C, Seipel P, Bai RY, Coutinho S et al. (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.
  5. ↑ 5.0 5.1 Bertagnolo V, Marchisio M, Brugnoli F, Bavelloni A, Boccafogli L, Colamussi ML et al. (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.
  6. ↑ 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. PMID 9200440. Vancouver style error (help)
  7. ↑ 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. PMC 231301. PMID 8649418.
  8. ↑ 8.0 8.1 Germani A, Romero F, Houlard M, Camonis J, Gisselbrecht S, Fischer S et al. (May 1999). "hSiah2 is a new Vav binding protein which inhibits Vav-mediated signaling pathways". Mol. Cell. Biol. 19 (5): 3798–807. PMC 84217. PMID 10207103.
  9. ↑ 9.0 9.1 9.2 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.
  10. ↑ 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. doi:10.1073/pnas.91.26.12629. PMC 45492. PMID 7809090.
  11. ↑ 11.0 11.1 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.
  12. ↑ 12.0 12.1 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.
  13. ↑ 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. PMC 398079. PMID 7530656.
  14. ↑ Romero F, Dargemont C, Pozo F, Reeves WH, Camonis J, Gisselbrecht S et al. (January 1996). "p95vav associates with the nuclear protein Ku-70". Mol. Cell. Biol. 16 (1): 37–44. PMC 230976. PMID 8524317.
  15. ↑ 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.
  16. ↑ Perez-Villar JJ, Whitney GS, Sitnick MT, Dunn RJ, Venkatesan S, O'Day K et al. (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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 19.0 19.1 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.
  20. ↑ 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. Vancouver style error (help)
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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