title: Redox-linked cell surface-oriented signaling for T-cell death.
abstract: T-cell death, which occurs either for ontogenic T-cell selection or for activated T-cell elimination, is normally induced through binding of a specific ligand to cell-surface T-cell receptor for crosslinkage. Heavy metals and carbonyl compounds that bind to protein-reactive groups such as cysteine sulfhydryl groups and lysine epsilon-amino groups may also induce crosslinkage of cell-surface proteins, in part replacing or modifying the ligand-mediated action. This chemical event has been found to accompany clustering of membrane rafts, to which signal-transducing elements such as glycosylphosphatidylinositol-anchored proteins and Src family protein tyrosine kinases (PTKs) are attached, and to trigger the signal transduction for apoptotic T-cell death, inducing mitochondrial membrane potential reduction, caspase activation and DNA fragmentation. As signals potentially upstream of this signaling, activations of PTKs and mitogen-activated protein (MAP) family kinases and production of reactive oxygen species (ROS) were induced following the cell-surface event, and crucial roles of activation of c-Jun amino-terminal kinase and apoptosis signal-regulating kinase 1 by a redox-linked mechanism in the cell-death signaling were demonstrated. Intriguingly, ROS production as well as PTK/MAP family kinase activation occurred in a membrane raft integrity-dependent manner. The redox-linked and cell surface-oriented signal delivery pathway demonstrated here may play an important role in induction of immune disorders by protein reactive group-binding chemicals.
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Anwarul A
authors.initials: AA
authors.lastname: Akhand
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Khaled
authors.initials: K
authors.lastname: Hossain
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyata
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nagase
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Suzuki
authors.forename: Izumi
authors.initials: I
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D011956:Receptors, Cell Surface; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases