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Sci. Signal., 15 December 2009
Vol. 2, Issue 101, p. ra83
[DOI: 10.1126/scisignal.2000420]
RESEARCH ARTICLES
Editor's Summary
Not All GEF All The Time
Vav1 is a guanine nucleotide exchange factor (GEF) that activates members of the Rho family of small guanosine triphosphatases (GTPases). Vav1 is an important mediator of T cell receptor (TCR) signaling and is required for the development of T cells in the thymus and for their activation and proliferation in response to antigen stimulation. TCR-stimulated remodeling of the actin cytoskeleton also requires Vav1; however, whether all of these functions of Vav1 require its GEF activity is unknown. Saveliev et al. generated mice that expressed a mutant Vav1 lacking GEF activity but that otherwise retained the properties of wild-type Vav1. Although the GEF activity of Vav1 was required for positive selection of CD4 and CD8 single-positive thymocytes and for T cell activation, other TCR- and Vav1-dependent processes were unaffected by the loss of its GEF activity, such as Ca2+ flux and activation of extracellular signal–regulated kinase (ERK). The authors suggest that Vav1 might play a role as an adaptor protein to mediate its GEF-independent functions, particularly for the activation of PLC-1.
Citation: A. Saveliev, L. Vanes, O. Ksionda, J. Rapley, S. J. Smerdon, K. Rittinger, V. L. J. Tybulewicz, Function of the Nucleotide Exchange Activity of Vav1 in T Cell Development and Activation. Sci. Signal.2, ra83 (2009).
Vav1 regulates MHCII expression in murine resting and activated B cells.
B. Jux, A. Staratschek-Jox, J. M. Penninger, J. L. Schultze, and W. Kolanus (2013)
Int. Immunol.
25, 307-317
|Abstract »|Full Text »|PDF »
The N-terminal 20-Amino Acid Region of Guanine Nucleotide Exchange Factor Vav1 Plays a Distinguished Role in T Cell Receptor-mediated Calcium Signaling.
S.-Y. Li, M.-J. Du, Y.-J. Wan, B. Lan, Y.-H. Liu, Y. Yang, C.-Z. Zhang, and Y. Cao (2013)
J. Biol. Chem.
288, 3777-3785
|Abstract »|Full Text »|PDF »
Mechanism and function of Vav1 localisation in TCR signalling.
O. Ksionda, A. Saveliev, R. Kochl, J. Rapley, M. Faroudi, J. E. Smith-Garvin, C. Wulfing, K. Rittinger, T. Carter, and V. L. J. Tybulewicz (2012)
J. Cell Sci.
125, 5302-5314
|Abstract »|Full Text »|PDF »
The Rho Exchange Factors Vav2 and Vav3 Control a Lung Metastasis-Specific Transcriptional Program in Breast Cancer Cells.
C. Citterio, M. Menacho-Marquez, R. Garcia-Escudero, R. M. Larive, O. Barreiro, F. Sanchez-Madrid, J. M. Paramio, and X. R. Bustelo (2012)
Science Signaling
5, ra71
|Abstract »|Full Text »|PDF »
Interchangeability of Themis1 and Themis2 in Thymocyte Development Reveals Two Related Proteins with Conserved Molecular Function.
R. Lesourne, E. Zvezdova, K.-D. Song, D. El-Khoury, S. Uehara, V. A. Barr, L. E. Samelson, and P. E. Love (2012)
J. Immunol.
189, 1154-1161
|Abstract »|Full Text »|PDF »
Complementary Phosphorylation Sites in the Adaptor Protein SLP-76 Promote Synergistic Activation of Natural Killer Cells.
Vav1 Oncogenic Mutation Inhibits T Cell Receptor-induced Calcium Mobilization through Inhibition of Phospholipase C{gamma}1 Activation.
M. Knyazhitsky, E. Moas, E. Shaginov, A. Luria, and A. Braiman (2012)
J. Biol. Chem.
287, 19725-19735
|Abstract »|Full Text »|PDF »
The p.Arg63Trp polymorphism controls Vav1 functions and Foxp3 regulatory T cell development.
C. Colacios, A. Casemayou, A. S. Dejean, F. Gaits-Iacovoni, C. Pedros, I. Bernard, D. Lagrange, M. Deckert, L. Lamouroux, M. Jagodic, et al. (2011)
J. Exp. Med.
208, 2183-2191
|Abstract »|Full Text »|PDF »
Two Closely Spaced Tyrosines Regulate NFAT Signaling in B Cells via Syk Association with Vav.
C.-H. Chen, V. A. Martin, N. M. Gorenstein, R. L. Geahlen, and C. B. Post (2011)
Mol. Cell. Biol.
31, 2984-2996
|Abstract »|Full Text »|PDF »
Impairment of Immunological Synapse Formation in Adaptively Tolerant T Cells.
Vav1-Mediated Scaffolding Interactions Stabilize SLP-76 Microclusters and Contribute to Antigen-Dependent T Cell Responses.
N. R. Sylvain, K. Nguyen, and S. C. Bunnell (2011)
Science Signaling
4, ra14
|Abstract »|Full Text »|PDF »
P-Rex1 and Vav1 Cooperate in the Regulation of Formyl-Methionyl-Leucyl-Phenylalanine-Dependent Neutrophil Responses.
C. D. Lawson, S. Donald, K. E. Anderson, D. T. Patton, and H. C. E. Welch (2011)
J. Immunol.
186, 1467-1476
|Abstract »|Full Text »|PDF »
Critical roles for Rac GTPases in T-cell migration to and within lymph nodes.
M. Faroudi, M. Hons, A. Zachacz, C. Dumont, R. Lyck, J. V. Stein, and V. L. J. Tybulewicz (2010)
Blood
116, 5536-5547
|Abstract »|Full Text »|PDF »
Fine Tuning of the Threshold of T Cell Selection by the Nck Adapters.
E. Roy, D. Togbe, A. Holdorf, D. Trubetskoy, S. Nabti, G. Kublbeck, S. Schmitt, A. Kopp-Schneider, F. Leithauser, P. Moller, et al. (2010)
J. Immunol.
185, 7518-7526
|Abstract »|Full Text »|PDF »
Vav3 Is Involved in GABAergic Axon Guidance Events Important for the Proper Function of Brainstem Neurons Controlling Cardiovascular, Respiratory, and Renal Parameters.
V. Sauzeau, J. A. C. Horta-Junior, A. S. Riolobos, G. Fernandez, M. A. Sevilla, D. E. Lopez, M. J. Montero, B. Rico, and X. R. Bustelo (2010)
Mol. Biol. Cell
21, 4251-4263
|Abstract »|Full Text »|PDF »
Phosphatidylinositol 3-Kinase Signaling in Thymocytes: The Need for Stringent Control.
E. Fayard, G. Moncayo, B. A. Hemmings, and G. A. Hollander (2010)
Science Signaling
3, re5
|Abstract »|Full Text »|PDF »
Tyrosine Residues at the Carboxyl Terminus of Vav1 Play an Important Role in Regulation of Its Biological Activity.
G. Lazer, L. Pe'er, M. Farago, K. Machida, B. J. Mayer, and S. Katzav (2010)
J. Biol. Chem.
285, 23075-23085
|Abstract »|Full Text »|PDF »
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