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.
Eischen
C M
CM
Department of Immunology, Mayo Clinic and Foundation, Rochester, MN 55905-0001, USA.
Williams
B L
BL
Zhang
W
W
Samelson
L E
LE
Lynch
D H
DH
Abraham
R T
RT
Leibson
P J
PJ
D017209:Apoptosis / Q000276:immunology*; D053222:Fas Ligand Protein; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human