ZAP-70 tyrosine kinase is required for the up-regulation of Fas ligand in activation-induced T cell apoptosis.
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.
Duke Scholars
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- fas Receptor
- ZAP-70 Protein-Tyrosine Kinase
- Up-Regulation
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- RNA, Messenger
- Protein-Tyrosine Kinases
- Membrane Glycoproteins
- Lymphocyte Activation
- Ligands
Citation
Published In
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- fas Receptor
- ZAP-70 Protein-Tyrosine Kinase
- Up-Regulation
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- RNA, Messenger
- Protein-Tyrosine Kinases
- Membrane Glycoproteins
- Lymphocyte Activation
- Ligands