Mechanism and function of Vav1 localization in TCR signaling

Olga Ksionda, Alexander Saveliev, Robert Köchl, Jonathan Rapley, Mustapha Faroudi, Jennifer E Smith-Garvin, Christoph Wülfing, Katrin Rittinger, Victor L J Tybulewicz, T Carter

Research output: Contribution to journalArticle (Academic Journal)

18 Citations (Scopus)

Abstract

The antigen-specific binding of T cells to antigen presenting cells results in recruitment of signaling 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 TCR signaling, 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 (SH3(B)) 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 SH3(B) domains of Vav1. Finally, we show that the same two domains are critical for the phosphorylation of Vav1 and its signaling 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.
Original languageEnglish
JournalJournal of Cell Science
DOIs
Publication statusPublished - 2012

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    Ksionda, O., Saveliev, A., Köchl, R., Rapley, J., Faroudi, M., Smith-Garvin, J. E., Wülfing, C., Rittinger, K., Tybulewicz, V. L. J., & Carter, T. (2012). Mechanism and function of Vav1 localization in TCR signaling. Journal of Cell Science. https://doi.org/10.1242/jcs.105148