Abstract
Activation-induced cell death (AICD) is initiated by the TCR-dependent up-regulation of Fas ligand (FasL) mRNA. The subsequently generated soluble or cell-associated FasL gene products bind Fas, leading to apoptosis of the T cells. Although TCR stimulation is essential to initiate AICD, little is known about which TCR-initiated second messengers are required for FasL expression. We provide evidence in this work that T cells lacking the tyrosine kinase ZAP-70 are unable to up-regulate FasL and undergo AICD. Transfection of wild-type ZAP-70 into the ZAP-70-deficient T cells restores their sensitivity to TCR-induced apoptosis, whereas transfection of catalytically inactive ZAP-70 does not. These results provide clear evidence that ZAP-70 tyrosine kinase is essential in up-regulating FasL for TCR-induced apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis / immunology*
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Fas Ligand Protein
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Humans
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Jurkat Cells
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Ligands
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Lymphocyte Activation*
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Protein-Tyrosine Kinases / deficiency
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Protein-Tyrosine Kinases / physiology*
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RNA, Messenger / biosynthesis
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Antigen, T-Cell / physiology*
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T-Lymphocytes / enzymology*
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Up-Regulation / immunology*
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ZAP-70 Protein-Tyrosine Kinase
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fas Receptor / biosynthesis
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fas Receptor / genetics
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fas Receptor / physiology*
Substances
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FASLG protein, human
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Fas Ligand Protein
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Ligands
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Membrane Glycoproteins
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RNA, Messenger
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Receptors, Antigen, T-Cell
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fas Receptor
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Protein-Tyrosine Kinases
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human