Skip to Main content Skip to Navigation
Journal articles

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.

Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [51 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-00162042
Contributor : Bérengère Hugot <>
Submitted on : Saturday, February 27, 2010 - 4:39:27 PM
Last modification on : Thursday, June 18, 2020 - 12:32:04 PM
Long-term archiving on: : Wednesday, November 30, 2016 - 9:20:17 AM

File

Dong_2006.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Shen Dong, Béatrice Corre, Elodie Foulon, E. Dufour, A. Veillette, et al.. 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.. The Journal of Experimental Medecine, The Rockefeller University Press, 2006, 203 (11), pp.2509-18. ⟨10.1084/jem.20060650⟩. ⟨pasteur-00162042⟩

Share

Metrics

Record views

377

Files downloads

504