Publication: Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub.

Publié dans: Nat Immunol 2014 Apr; 15(4): 384-392

Auteurs: Roncagalli R, Hauri S, Fiore F, Liang Y, Chen Z, Sansoni A, Kanduri K, Joly R, Malzac A, Lähdesmäki H, Lahesmaa R, Yamasaki S, Saito T, Malissen M, Aebersold R, Gstaiger M, Malissen B

Résumé

T cell antigen receptor (TCR)-mediated activation of T cells requires the interaction of dozens of proteins. Here we used quantitative mass spectrometry and activated primary CD4(+) T cells from mice in which a tag for affinity purification was knocked into several genes to determine the composition and dynamics of multiprotein complexes that formed around the kinase Zap70 and the adaptors Lat and SLP-76. Most of the 112 high-confidence time-resolved protein interactions we observed were previously unknown. The surface receptor CD6 was able to initiate its own signaling pathway by recruiting SLP-76 and the guanine nucleotide-exchange factor Vav1 regardless of the presence of Lat. Our findings provide a more complete model of TCR signaling in which CD6 constitutes a signaling hub that contributes to the diversification of TCR signaling.

Lien vers Pubmed [PMID] – 24584089

Lien vers le DOI – 10.1038/ni.2843