First Author | Roncagalli R | Year | 2014 |
Journal | Nat Immunol | Volume | 15 |
Issue | 4 | Pages | 384-392 |
PubMed ID | 24584089 | Mgi Jnum | J:209882 |
Mgi Id | MGI:5568870 | Doi | 10.1038/ni.2843 |
Citation | Roncagalli R, et al. (2014) Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub. Nat Immunol 15(4):384-392 |
abstractText | 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. |