Redox-linked cell surface-oriented signaling for T-cell death.
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.
Akhand
Anwarul A
AA
Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Du
Jun
J
Liu
Wei
W
Hossain
Khaled
K
Miyata
Toshio
T
Nagase
Fumihiko
F
Kato
Masashi
M
Suzuki
Haruhiko
H
Nakashima
Izumi
I
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*
D011956:Receptors, Cell Surface; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases