Publication: Serine residues in the LAT adaptor are essential for TCR-dependent signal transduction
Loading...
Date
2010-09-10
Authors
Martínez Florensa, Mario ; García Blesa, Antonio ; Yélamos, José ; Muñoz Suano, Alba ; Domínguez Villar, Margarita ; Alonso, Antonio ; García Cózar, Francisco ; Aparicio, Pedro ; Malissen, Bernard ; Aguado, Enrique ; Valdor Alonso, Rut
item.page.secondaryauthor
item.page.director
Publisher
Wiley
publication.page.editor
publication.page.department
DOI
https://doi.org/ 10.1189/jlb.0509342
item.page.type
info:eu-repo/semantics/article
Description
©2010. This document is the Publishes version of a Published Work that appeared in final form in Journal of Leukocyte Biology (JLB). To access the final edited and published work see https://doi.org/ 10.1189/jlb.0509342
Abstract
The adaptor protein LAT has a prominent role in the transduction of intracellular signals elicited by the TCR/CD3 complex. Upon TCR engagement, LAT becomes tyrosine-phosphorylated and thereby, recruits to the membrane several proteins implicated in the activation of downstream signaling pathways. However, little is known about the role of other conserved motifs present in the LAT sequence. Here, we report that the
adaptor LAT contains several conserved serine-based motifs, which are essential for proper signal transduction through the TCR. Mutation of these serine motifs in the human T cell line Jurkat prevents proper calcium
influx, MAPK activation, and IL-2 production in response to TCR/CD3 stimulation. Moreover, this mutant form of LAT has a reduced ability to bind to PLC- 1 and SLP-76, although phosphorylation of tyrosine residues 132, 171, and 191 is not decreased, raising a possible role for the serine-based motifs of LAT for the binding of important partners. The functional role of LAT serine-based motifs in signal transduction could be mediated by an effect on tyrosine phosphorylation, as their mutation significantly diminishes the phosphorylation of tyrosine residue 226. In addition, these serine motifs seem to have a regulatory role, given that upon their mutation, ZAP-70 shows enhanced phosphorylation. Therefore, the LAT serine-based motifs likely regulate signaling pathways that are essential for T cell physiology. J.
Leukoc. Biol. 89: 63–73; 2011.
publication.page.subject
Citation
Journal of Leukocyte Biology, 89, 2011:63-73
item.page.embargo
Collections
Ir a Estadísticas
Sin licencia Creative Commons.