ZAP-70 tyrosine kinase is required for the up-regulation of Fas ligand in activation-induced T cell apoptosis.

Eischen CM, Williams BL, Zhang W, Samelson LE, Lynch DH, Abraham RT, Leibson PJ
J Immunol. 1997 159 (3): 1135-9

PMID: 9233606

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.

MeSH Terms (14)

Apoptosis Fas Ligand Protein fas Receptor Humans Jurkat Cells Ligands Lymphocyte Activation Membrane Glycoproteins Protein-Tyrosine Kinases Receptors, Antigen, T-Cell RNA, Messenger T-Lymphocytes Up-Regulation ZAP-70 Protein-Tyrosine Kinase

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