title: Combinatorial proteomic analysis of intercellular signaling applied to the CD28 T-cell costimulatory receptor.
abstract: Systematic characterization of intercellular signaling approximating the physiological conditions of stimulation that involve direct cell-cell contact is challenging. We describe a proteomic strategy to analyze physiological signaling mediated by the T-cell costimulatory receptor CD28. We identified signaling pathways activated by CD28 during direct cell-cell contact by global analysis of protein phosphorylation. To define immediate CD28 targets, we used phosphorylated forms of the CD28 cytoplasmic region to obtain the CD28 interactome. The interaction profiles of selected CD28-interacting proteins were further characterized in vivo for amplifying the CD28 interactome. The combination of the global phosphorylation and interactome analyses revealed broad regulation of CD28 and its interactome by phosphorylation. Among the cellular phosphoproteins influenced by CD28 signaling, CapZ-interacting protein (CapZIP), a regulator of the actin cytoskeleton, was implicated by functional studies. The combinatorial approach applied herein is widely applicable for characterizing signaling networks associated with membrane receptors with short cytoplasmic tails.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5; Department of Chemistry and Shenzhen Key Laboratory of Cell Microenvironment, South University of Science and Technology of China, Shenzhen 518055, China; aweiss@medicine.ucsf.edu tian.rj@sustc.edu.cn.
authors.forename: Ruijun
authors.initials: R
authors.lastname: Tian
authors.affiliation: Division of Rheumatology, Department of Medicine, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, and.
authors.forename: Haopeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;
authors.forename: Gerald D
authors.initials: GD
authors.lastname: Gish
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;
authors.forename: Evangelia
authors.initials: E
authors.lastname: Petsalaki
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;
authors.forename: Adrian
authors.initials: A
authors.lastname: Pasculescu
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037;
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Division of Rheumatology, Department of Medicine, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, and.
authors.forename: Marianne
authors.initials: M
authors.lastname: Mollenauer
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;
authors.forename: Richard D
authors.initials: RD
authors.lastname: Bagshaw
authors.affiliation: Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA 94720; and.
authors.forename: Nir
authors.initials: N
authors.lastname: Yosef
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037;
authors.forename: Tony
authors.initials: T
authors.lastname: Hunter
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada M5S 1A8.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gingras
authors.affiliation: Division of Rheumatology, Department of Medicine, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, and Howard Hughes Medical Institute, University of California, San Francisco, CA 94143; aweiss@medicine.ucsf.edu tian.rj@sustc.edu.cn.
authors.forename: Arthur
authors.initials: A
authors.lastname: Weiss
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada M5S 1A8.
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
mesh_terms: D000199:Actins / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism*; D002450:Cell Communication; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D019169:Jurkat Cells; D013058:Mass Spectrometry; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D040901:Proteomics; D018000:Receptors, Peptide / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000199:Actins; D018106:CD28 Antigens; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D018000:Receptors, Peptide
keywords: T cells; intercellular signaling; phosphorylation; proteomics; signal transduction
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