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Mechanism and function of Vav1 localisation in TCR signalling

Ksionda, O; Saveliev, A; Köchl, R; Rapley, J; Faroudi, M; Smith-Garvin, JE; Wülfing, C; Rittinger, K; Carter, T; Tybulewicz, VL (2012) Mechanism and function of Vav1 localisation in TCR signalling. JOURNAL OF CELL SCIENCE, 125 (22). 5302 - 5314 (13). ISSN 0021-9533 https://doi.org/10.1242/jcs.105148
SGUL Authors: Carter, Thomas David

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Abstract

The antigen-specific binding of T cells to antigen presenting cells results in recruitment of signalling proteins to microclusters at the cell-cell interface known as the immunological synapse (IS). The Vav1 guanine nucleotide exchange factor plays a critical role in T cell antigen receptor (TCR) signalling, leading to the activation of multiple pathways. We now show that it is recruited to microclusters and to the IS in primary CD4+ and CD8+ T cells. Furthermore, we show that this recruitment depends on the SH2 and C-terminal SH3 (SH3B) domains of Vav1, and on phosphotyrosines 112 and 128 of the SLP76 adaptor protein. Biophysical measurements show that Vav1 binds directly to these residues on SLP76 and that efficient binding depends on the SH2 and SH3B domains of Vav1. Finally, we show that the same two domains are critical for the phosphorylation of Vav1 and its signalling function in TCR-induced calcium flux. We propose that Vav1 is recruited to the IS by binding to SLP76 and that this interaction is critical for the transduction of signals leading to calcium flux.

Item Type: Article
Additional Information: © 2012. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0/), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms.
Keywords: Animals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Calcium, Cells, Cultured, Humans, Immunological Synapses, Mice, Mutant Proteins, Phosphorylation, Protein Transport, Proto-Oncogene Proteins c-vav, Receptors, Antigen, T-Cell, Signal Transduction, src Homology Domains, Science & Technology, Life Sciences & Biomedicine, Cell Biology, CELL BIOLOGY, Immunological synapse, T cell, Signal transduction, SLP76, Vav1, T-CELL-RECEPTOR, SUPRAMOLECULAR ACTIVATION CLUSTER, NUCLEOTIDE EXCHANGE ACTIVITY, IMMUNOLOGICAL SYNAPSE, ACTIN CYTOSKELETON, ANTIGEN RECEPTOR, TRANSGENIC MICE, TYROSINE PHOSPHORYLATION, PHOSPHOLIPASE C-GAMMA-1, NEGATIVE SELECTION
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: JOURNAL OF CELL SCIENCE
ISSN: 0021-9533
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Dates:
DateEvent
15 November 2012Published
Web of Science ID: WOS:000314511900007
Download EPMC Full text (HTML)
URI: https://openaccess.sgul.ac.uk/id/eprint/103589
Publisher's version: https://doi.org/10.1242/jcs.105148

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