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Sci. Signal., 8 March 2011
Vol. 4, Issue 163, p. ra14
[DOI: 10.1126/scisignal.2001178]


Editor's Summary

More than the Sum of Its Parts
Vav1 is a guanine nucleotide exchange factor (GEF) that is required for transducing signals from the T cell receptor (TCR). Vav1 synergizes with the adaptor protein SLP-76, which forms microclusters in activated T cells, and disruption of these microclusters inhibits T cell activation. Sylvain et al. performed live-cell imaging and functional analysis of antigen-stimulated cells expressing various mutant Vav1 proteins. The C terminus of Vav1 contains Src homology domains, and the N terminus contains a calponin homology domain and the GEF domain. The C terminus of Vav1 was required for the recruitment of Vav1 into SLP-76 microclusters but was not sufficient to stabilize the microclusters. Although the GEF activity of Vav1 was required for TCR signaling, stabilization of the microclusters was not affected by activation or inactivation of the GEF activity Vav1; this finding suggests that Vav1 enhances TCR signaling through its GEF activity and by increasing the persistence of SLP-76 microclusters through multiple scaffolding interactions.

Citation: N. R. Sylvain, K. Nguyen, S. C. Bunnell, Vav1-Mediated Scaffolding Interactions Stabilize SLP-76 Microclusters and Contribute to Antigen-Dependent T Cell Responses. Sci. Signal. 4, ra14 (2011).

Read the Full Text

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   Abstract »    Full Text »    PDF »
Multipoint Binding of the SLP-76 SH2 Domain to ADAP Is Critical for Oligomerization of SLP-76 Signaling Complexes in Stimulated T Cells.
N. P. Coussens, R. Hayashi, P. H. Brown, L. Balagopalan, A. Balbo, I. Akpan, J. C. D. Houtman, V. A. Barr, P. Schuck, E. Appella, et al. (2013)
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Activation of Extracellular Signal-Regulated Kinase but Not of p38 Mitogen-Activated Protein Kinase Pathways in Lymphocytes Requires Allosteric Activation of SOS.
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Modulation of T cell signaling by the actin cytoskeleton.
Y. Yu, A. A. Smoligovets, and J. T. Groves (2013)
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   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)
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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)
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   Abstract »    Full Text »    PDF »
HIV-1 Nef Limits Communication between Linker of Activated T Cells and SLP-76 To Reduce Formation of SLP-76-Signaling Microclusters following TCR Stimulation.
L. Abraham, P. Bankhead, X. Pan, U. Engel, and O. T. Fackler (2012)
J. Immunol. 189, 1898-1910
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Vav1 Oncogenic Mutation Inhibits T Cell Receptor-induced Calcium Mobilization through Inhibition of Phospholipase C{gamma}1 Activation.
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   Abstract »    Full Text »    PDF »

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