title: Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub.
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.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Marseille, France.|INSERM U1104, Marseille, France.|CNRS UMR7280, Marseille, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Roncagalli
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.|Competence Center for Systems Physiology and Metabolic Diseases, ETH Zurich, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Hauri
authors.affiliation: Centre d'Immunophénomique, UM2 Aix-Marseille Université, Marseille, France.|INSERM US012, Marseille, France.|CNRS UMS3367, Marseille, France.
authors.forename: Fréderic
authors.initials: F
authors.lastname: Fiore
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Marseille, France.|INSERM U1104, Marseille, France.|CNRS UMR7280, Marseille, France.
authors.forename: Yinming
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Centre d'Immunophénomique, UM2 Aix-Marseille Université, Marseille, France.|INSERM US012, Marseille, France.|CNRS UMS3367, Marseille, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Sansoni
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland.
authors.forename: Kartiek
authors.initials: K
authors.lastname: Kanduri
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Marseille, France.|INSERM U1104, Marseille, France.|CNRS UMR7280, Marseille, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Joly
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Marseille, France.|INSERM U1104, Marseille, France.|CNRS UMR7280, Marseille, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Malzac
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland.|Department of Information and Computer Science, Aalto University, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Lähdesmäki
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Marseille, France.|INSERM U1104, Marseille, France.|CNRS UMR7280, Marseille, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Malissen
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.|Faculty of Science, University of Zurich, Zurich, Switzerland.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.|Competence Center for Systems Physiology and Metabolic Diseases, ETH Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gstaiger
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Marseille, France.|INSERM U1104, Marseille, France.|CNRS UMR7280, Marseille, France.|Centre d'Immunophénomique, UM2 Aix-Marseille Université, Marseille, France.|INSERM US012, Marseille, France.|CNRS UMS3367, Marseille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D020013:Calcium Signaling / Q000235:genetics; D002478:Cells, Cultured; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D040901:Proteomics; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; C491734:Lat protein, mouse; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; C092947:SLP-76 signal Transducing adaptor proteins; C496619:Vav1 protein, mouse; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse