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Nat Immunol. 2014 Apr;15(4):384-92. doi: 10.1038/ni.2843. Epub 2014 Mar 2.

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

Author information

  • 11] Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Marseille, France. [2] INSERM U1104, Marseille, France. [3] Centre National de la Recherche Scientifique UMR7280, Marseille, France. [4].
  • 21] Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule Zurich, Zurich, Switzerland. [2] Competence Center for Systems Physiology and Metabolic Diseases, Eidgenossische Technische Hochschule Zurich, Zurich, Switzerland. [3].
  • 31] Centre d'Immunophénomique, UM2 Aix-Marseille Université, Marseille, France. [2] INSERM US012, Marseille, France. [3] CNRS UMS3367, Marseille, France.
  • 41] Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Marseille, France. [2] INSERM U1104, Marseille, France. [3] Centre National de la Recherche Scientifique UMR7280, Marseille, France.
  • 5Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland.
  • 61] Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland. [2] Department of Information and Computer Science, Aalto University, Aalto, Finland.
  • 7Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
  • 8RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • 91] Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule Zurich, Zurich, Switzerland. [2] Competence Center for Systems Physiology and Metabolic Diseases, Eidgenossische Technische Hochschule Zurich, Zurich, Switzerland. [3] Faculty of Science, University of Zurich, Zurich, Switzerland.
  • 101] Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule Zurich, Zurich, Switzerland. [2] Competence Center for Systems Physiology and Metabolic Diseases, Eidgenossische Technische Hochschule Zurich, Zurich, Switzerland.
  • 111] Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Marseille, France. [2] INSERM U1104, Marseille, France. [3] Centre National de la Recherche Scientifique UMR7280, Marseille, France. [4] Centre d'Immunophénomique, UM2 Aix-Marseille Université, Marseille, France. [5] INSERM US012, Marseille, France. [6] CNRS UMS3367, Marseille, France.

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.

PMID:
24584089
[PubMed - indexed for MEDLINE]
PMCID:
PMC4037560
Free PMC Article
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