Cargando…

T cell receptor for antigen induces linker for activation of T cell–dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2

Adaptor proteins positively or negatively regulate the T cell receptor for antigen (TCR) signaling cascade. We report that after TCR stimulation, the inhibitory adaptor downstream of kinase (Dok)-2 and its homologue Dok-1 are involved in a multimolecular complex including the lipid phosphatase Src h...

Descripción completa

Detalles Bibliográficos
Autores principales: Dong, Shen, Corre, Béatrice, Foulon, Eliane, Dufour, Evelyne, Veillette, André, Acuto, Oreste, Michel, Frédérique
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118126/
https://www.ncbi.nlm.nih.gov/pubmed/17043143
http://dx.doi.org/10.1084/jem.20060650
_version_ 1782140954374832128
author Dong, Shen
Corre, Béatrice
Foulon, Eliane
Dufour, Evelyne
Veillette, André
Acuto, Oreste
Michel, Frédérique
author_facet Dong, Shen
Corre, Béatrice
Foulon, Eliane
Dufour, Evelyne
Veillette, André
Acuto, Oreste
Michel, Frédérique
author_sort Dong, Shen
collection PubMed
description Adaptor proteins positively or negatively regulate the T cell receptor for antigen (TCR) signaling cascade. We report that after TCR stimulation, the inhibitory adaptor downstream of kinase (Dok)-2 and its homologue Dok-1 are involved in a multimolecular complex including the lipid phosphatase Src homology 2 domain–containing inositol polyphosphate 5′-phosphatase (SHIP)-1 and Grb-2 which interacts with the membrane signaling scaffold linker for activation of T cells (LAT). Knockdown of LAT and SHIP-1 expression indicated that SHIP-1 favored recruitment of Dok-2 to LAT. Knockdown of Dok-2 and Dok-1 revealed their negative control on Akt and, unexpectedly, on Zap-70 activation. Our findings support the view that Dok-1 and -2 are critical elements of a LAT-dependent negative feedback loop that attenuates early TCR signal. Dok-1 and -2 may therefore exert a critical role in shaping the immune response and as gatekeepers for T cell tolerance.
format Text
id pubmed-2118126
institution National Center for Biotechnology Information
language English
publishDate 2006
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21181262007-12-13 T cell receptor for antigen induces linker for activation of T cell–dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2 Dong, Shen Corre, Béatrice Foulon, Eliane Dufour, Evelyne Veillette, André Acuto, Oreste Michel, Frédérique J Exp Med Articles Adaptor proteins positively or negatively regulate the T cell receptor for antigen (TCR) signaling cascade. We report that after TCR stimulation, the inhibitory adaptor downstream of kinase (Dok)-2 and its homologue Dok-1 are involved in a multimolecular complex including the lipid phosphatase Src homology 2 domain–containing inositol polyphosphate 5′-phosphatase (SHIP)-1 and Grb-2 which interacts with the membrane signaling scaffold linker for activation of T cells (LAT). Knockdown of LAT and SHIP-1 expression indicated that SHIP-1 favored recruitment of Dok-2 to LAT. Knockdown of Dok-2 and Dok-1 revealed their negative control on Akt and, unexpectedly, on Zap-70 activation. Our findings support the view that Dok-1 and -2 are critical elements of a LAT-dependent negative feedback loop that attenuates early TCR signal. Dok-1 and -2 may therefore exert a critical role in shaping the immune response and as gatekeepers for T cell tolerance. The Rockefeller University Press 2006-10-30 /pmc/articles/PMC2118126/ /pubmed/17043143 http://dx.doi.org/10.1084/jem.20060650 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Dong, Shen
Corre, Béatrice
Foulon, Eliane
Dufour, Evelyne
Veillette, André
Acuto, Oreste
Michel, Frédérique
T cell receptor for antigen induces linker for activation of T cell–dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2
title T cell receptor for antigen induces linker for activation of T cell–dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2
title_full T cell receptor for antigen induces linker for activation of T cell–dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2
title_fullStr T cell receptor for antigen induces linker for activation of T cell–dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2
title_full_unstemmed T cell receptor for antigen induces linker for activation of T cell–dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2
title_short T cell receptor for antigen induces linker for activation of T cell–dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2
title_sort t cell receptor for antigen induces linker for activation of t cell–dependent activation of a negative signaling complex involving dok-2, ship-1, and grb-2
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118126/
https://www.ncbi.nlm.nih.gov/pubmed/17043143
http://dx.doi.org/10.1084/jem.20060650
work_keys_str_mv AT dongshen tcellreceptorforantigeninduceslinkerforactivationoftcelldependentactivationofanegativesignalingcomplexinvolvingdok2ship1andgrb2
AT correbeatrice tcellreceptorforantigeninduceslinkerforactivationoftcelldependentactivationofanegativesignalingcomplexinvolvingdok2ship1andgrb2
AT fouloneliane tcellreceptorforantigeninduceslinkerforactivationoftcelldependentactivationofanegativesignalingcomplexinvolvingdok2ship1andgrb2
AT dufourevelyne tcellreceptorforantigeninduceslinkerforactivationoftcelldependentactivationofanegativesignalingcomplexinvolvingdok2ship1andgrb2
AT veilletteandre tcellreceptorforantigeninduceslinkerforactivationoftcelldependentactivationofanegativesignalingcomplexinvolvingdok2ship1andgrb2
AT acutooreste tcellreceptorforantigeninduceslinkerforactivationoftcelldependentactivationofanegativesignalingcomplexinvolvingdok2ship1andgrb2
AT michelfrederique tcellreceptorforantigeninduceslinkerforactivationoftcelldependentactivationofanegativesignalingcomplexinvolvingdok2ship1andgrb2