Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor–independent TCR signaling hub
Copyright policy )Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor–independent TCR signaling hub
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.
- Kyushu University Japan
- University of Turku Finland
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE France
- Institute for Molecular Systems Biology Switzerland
- French National Centre for Scientific Research France
Antigens, Differentiation, T-Lymphocyte, CD4-Positive T-Lymphocytes, Proteomics, ZAP-70 Protein-Tyrosine Kinase, ta1182, Receptors, Antigen, T-Cell, Membrane Proteins, Mice, Transgenic, Phosphoproteins, Mice, Inbred C57BL, Mice, Antigens, CD, T-Lymphocyte Subsets, Multiprotein Complexes, Animals, Calcium Signaling, Proto-Oncogene Proteins c-vav, Cells, Cultured, Adaptor Proteins, Signal Transducing, Protein Binding
Antigens, Differentiation, T-Lymphocyte, CD4-Positive T-Lymphocytes, Proteomics, ZAP-70 Protein-Tyrosine Kinase, ta1182, Receptors, Antigen, T-Cell, Membrane Proteins, Mice, Transgenic, Phosphoproteins, Mice, Inbred C57BL, Mice, Antigens, CD, T-Lymphocyte Subsets, Multiprotein Complexes, Animals, Calcium Signaling, Proto-Oncogene Proteins c-vav, Cells, Cultured, Adaptor Proteins, Signal Transducing, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).115 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!