title: Integrative Proteomics and Phosphoproteomics Profiling Reveals Dynamic Signaling Networks and Bioenergetics Pathways Underlying T Cell Activation.
abstract: The molecular circuits by which antigens activate quiescent T cells remain poorly understood. We combined temporal profiling of the whole proteome and phosphoproteome via multiplexed isobaric labeling proteomics technology, computational pipelines for integrating multi-omics datasets, and functional perturbation to systemically reconstruct regulatory networks underlying T cell activation. T cell receptors activated the T cell proteome and phosphoproteome with discrete kinetics, marked by early dynamics of phosphorylation and delayed ribosome biogenesis and mitochondrial activation. Systems biology analyses identified multiple functional modules, active kinases, transcription factors and connectivity between them, and mitochondrial pathways including mitoribosomes and complex IV. Genetic perturbation revealed physiological roles for mitochondrial enzyme COX10-mediated oxidative phosphorylation in T cell quiescence exit. Our multi-layer proteomics profiling, integrative network analysis, and functional studies define landscapes of the T cell proteome and phosphoproteome and reveal signaling and bioenergetics pathways that mediate lymphocyte exit from quiescence.
authors.affiliation: Departments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.affiliation: Departments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Shaw
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Daniel Bastardo
authors.initials: DB
authors.lastname: Blanco
authors.affiliation: St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Wang
authors.affiliation: St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Ji-Hoon
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Departments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Sherri
authors.initials: S
authors.lastname: Rankin
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Cliff
authors.initials: C
authors.lastname: Guy
authors.affiliation: Departments of Structural Biology and Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; St. Jude Proteomics Facility, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: junmin.peng@stjude.org.
authors.forename: Junmin
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: hongbo.chi@stjude.org.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chi
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000276:immunology; D000818:Animals; D004734:Energy Metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D040901:Proteomics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D019883:Alkyl and Aryl Transferases; C512252:COX10 protein, mouse
keywords: T cell; glycolysis; kinase; mTORC1; mitochondria; phosphoproteomics; proteomics; quiescence exit; systems biology; systems immunology