VAV2 explained

Guanine nucleotide exchange factor VAV2 is a protein that in humans is encoded by the VAV2 gene.^{[1] [2]}

VAV2 is the second member of the VAV oncogene family. Unlike VAV1, which is expressed exclusively in hematopoietic cells, VAV2 transcripts were found in most tissues.^[2]

Interactions

VAV2 is a GEF for RAC1, specifically in fibroblasts VAV2 is necessary for integrin, but not growth factor–dependent activation of RAC leading to lamellipodia formation.^[3] Double DH domain mutations, L342R/L343SVav2 function as a dominant negative, blocking VAV2 GEF activity for RAC1 and a PH domain mutant is required for recruitment of VAV2 to the membrane in order to elicit GEF activity. VAV2 has also been shown to regulate collagen phagocytosis in a RAC1-dependent manner^[4] and interact with CD19^[5] and Grb2.^{[6] [7]}

Further reading

• Romero F, Fischer S . Structure and function of vav. . Cell. Signal. . 8 . 8 . 545–53 . 1997 . 9115846 . 10.1016/S0898-6568(96)00118-0 .
• Smit L, van der Horst G, Borst J . Sos, Vav, and C3G participate in B cell receptor-induced signaling pathways and differentially associate with Shc-Grb2, Crk, and Crk-L adaptors. . J. Biol. Chem. . 271 . 15 . 8564–9 . 1996 . 8621483 . 10.1074/jbc.271.15.8564 . free .
• Tamma SM, Chirmule N, Yagura H, etal . CD4 cross-linking (CD4XL) induces RAS activation and tumor necrosis factor-alpha secretion in CD4+ T cells. . Blood . 90 . 4 . 1588–93 . 1997 . 9269777 . 10.1182/blood.V90.4.1588. free .
• De Sepulveda P, Okkenhaug K, Rose JL, etal . Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation. . EMBO J. . 18 . 4 . 904–15 . 1999 . 10022833 . 10.1093/emboj/18.4.904 . 1171183 .
• Pandey A, Podtelejnikov AV, Blagoev B, etal . Analysis of receptor signaling pathways by mass spectrometry: identification of vav-2 as a substrate of the epidermal and platelet-derived growth factor receptors. . Proc. Natl. Acad. Sci. U.S.A. . 97 . 1 . 179–84 . 2000 . 10618391 . 10.1073/pnas.97.1.179 . 26636 . 2000PNAS...97..179P . free .
• Moores SL, Selfors LM, Fredericks J, etal . Vav family proteins couple to diverse cell surface receptors. . Mol. Cell. Biol. . 20 . 17 . 6364–73 . 2000 . 10938113 . 10.1128/MCB.20.17.6364-6373.2000 . 86111 .
• Liu BP, Burridge K . Vav2 activates Rac1, Cdc42, and RhoA downstream from growth factor receptors but not beta1 integrins. . Mol. Cell. Biol. . 20 . 19 . 7160–9 . 2000 . 10982832 . 10.1128/MCB.20.19.7160-7169.2000 . 86269 .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination. . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 10.1101/gr.143000 . 310948 .
• Doody GM, Billadeau DD, Clayton E, etal . Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes. . EMBO J. . 19 . 22 . 6173–84 . 2001 . 11080163 . 10.1093/emboj/19.22.6173 . 305817 .
• Tartare-Deckert S, Monthouel MN, Charvet C, etal . Vav2 activates c-fos serum response element and CD69 expression but negatively regulates nuclear factor of activated T cells and interleukin-2 gene activation in T lymphocyte. . J. Biol. Chem. . 276 . 24 . 20849–57 . 2001 . 11262396 . 10.1074/jbc.M010588200 . free .
• Teckchandani AM, Feshchenko EA, Tsygankov AY . c-Cbl facilitates fibronectin matrix production by v-Abl-transformed NIH3T3 cells via activation of small GTPases. . Oncogene . 20 . 14 . 1739–55 . 2001 . 11313921 . 10.1038/sj.onc.1204246 . 28410819 .
• Jevremovic D, Billadeau DD, Schoon RA, etal . Regulation of NK cell-mediated cytotoxicity by the adaptor protein 3BP2. . J. Immunol. . 166 . 12 . 7219–28 . 2001 . 11390470 . 10.4049/jimmunol.166.12.7219. free .
• Marignani PA, Carpenter CL . Vav2 is required for cell spreading. . J. Cell Biol. . 154 . 1 . 177–86 . 2001 . 11448999 . 10.1083/jcb.200103134 . 2196856 .
• Tamás P, Solti Z, Buday L . Membrane-targeting is critical for the phosphorylation of Vav2 by activated EGF receptor. . Cell. Signal. . 13 . 7 . 475–81 . 2001 . 11516622 . 10.1016/S0898-6568(01)00172-3 .
• Bourguignon LY, Zhu H, Zhou B, etal . Hyaluronan promotes CD44v3-Vav2 interaction with Grb2-p185(HER2) and induces Rac1 and Ras signaling during ovarian tumor cell migration and growth. . J. Biol. Chem. . 276 . 52 . 48679–92 . 2002 . 11606575 . 10.1074/jbc.M106759200 . free.
• Booden MA, Campbell SL, Der CJ . Critical but distinct roles for the pleckstrin homology and cysteine-rich domains as positive modulators of Vav2 signaling and transformation. . Mol. Cell. Biol. . 22 . 8 . 2487–97 . 2002 . 11909943 . 10.1128/MCB.22.8.2487-2497.2002 . 133724 .
• Tamás P, Solti Z, Bauer P, etal . Mechanism of epidermal growth factor regulation of Vav2, a guanine nucleotide exchange factor for Rac. . J. Biol. Chem. . 278 . 7 . 5163–71 . 2003 . 12454019 . 10.1074/jbc.M207555200 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .

Notes and References

1. Henske EP, Short MP, Jozwiak S, Bovey CM, Ramlakhan S, Haines JL, Kwiatkowski DJ . Identification of VAV2 on 9q34 and its exclusion as the tuberous sclerosis gene TSC1 . Ann Hum Genet . 59 . Pt 1 . 25–37 . June 1995 . 7762982 . 10.1111/j.1469-1809.1995.tb01603.x . 27548854 .
2. Web site: Entrez Gene: VAV2 vav 2 oncogene.
3. Marignani . Paola A . Kanai . Fumihiko . 2001-07-09 . Vav2 is required for cell spreading . The Journal of Cell Biology . en . 154 . 1 . 177–186 . 10.1083/jcb.200103134 . 0021-9525 . 11448999. 2196856 .
4. Arora . P. D. . Marignani . P. A. . McCulloch . C. A. . July 2008 . Collagen phagocytosis is regulated by the guanine nucleotide exchange factor Vav2 . American Journal of Physiology. Cell Physiology . en . 295 . 1 . C130–C137 . 10.1152/ajpcell.00168.2008 . 0363-6143 . 2493554 . 18434624.
5. Doody . G M . Billadeau D D . Clayton E . Hutchings A . Berland R . McAdam S . Leibson P J . Turner M . November 2000 . Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes . EMBO J. . 19 . 22 . 6173–84 . 0261-4189. 11080163 . 10.1093/emboj/19.22.6173 . 305817 .
6. Blagoev . Blagoy . Kratchmarova Irina . Ong Shao-En . Nielsen Mogens . Foster Leonard J . Mann Matthias . March 2003 . A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling . Nat. Biotechnol. . 21 . 3 . 315–8 . 1087-0156. 12577067 . 10.1038/nbt790 . 26838266 .
7. Bourguignon . L Y . Zhu H . Zhou B . Diedrich F . Singleton P A . Hung M C . Dec 2001 . Hyaluronan promotes CD44v3-Vav2 interaction with Grb2-p185(HER2) and induces Rac1 and Ras signaling during ovarian tumor cell migration and growth . J. Biol. Chem. . 276 . 52 . 48679–92 . 0021-9258. 11606575 . 10.1074/jbc.M106759200 . free.