%0 Journal Article %T 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. %+ Immunologie Moléculaire %+ McGill University = Université McGill [Montréal, Canada] %A Dong, Shen %A Corre, Béatrice %A Foulon, Elodie %A Dufour, E. %A Veillette, A. %A Acuto, Oreste %A Michel, Frédérique %< avec comité de lecture %@ 0022-1007 %J Journal of Experimental Medicine %I Rockefeller University Press %V 203 %N 11 %P 2509-18 %8 2006-10-30 %D 2006 %R 10.1084/jem.20060650 %M 17043143 %Z Life Sciences [q-bio]/ImmunologyJournal articles %X 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. %G English %2 https://pasteur.hal.science/pasteur-00162042/document %2 https://pasteur.hal.science/pasteur-00162042/file/Dong_2006.pdf %L pasteur-00162042 %U https://pasteur.hal.science/pasteur-00162042 %~ PASTEUR %~ CNRS %~ RIIP_PARIS