Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Antigens, CD / metabolism*
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Antigens, Differentiation, T-Lymphocyte / metabolism*
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CD4-Positive T-Lymphocytes / immunology*
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Calcium Signaling / genetics
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Cells, Cultured
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Multiprotein Complexes / metabolism
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Protein Binding / genetics
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Proteomics
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Proto-Oncogene Proteins c-vav / metabolism
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocyte Subsets / immunology*
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ZAP-70 Protein-Tyrosine Kinase / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD6 antigen
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Lat protein, mouse
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Membrane Proteins
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Multiprotein Complexes
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Phosphoproteins
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Proto-Oncogene Proteins c-vav
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Receptors, Antigen, T-Cell
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SLP-76 signal Transducing adaptor proteins
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Vav1 protein, mouse
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ZAP-70 Protein-Tyrosine Kinase
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Zap70 protein, mouse