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 Pas ligand (Fast) mRNA., The subsequently generated soluble or cell-associated Fast gene products bind Pas, leading to apo ptosis of the T cells, Although TCR stimulation is essential to initia te AICD, little is known about which TCR-initiated second messengers a re required for Fast expression, We provide evidence in this work that T cells lacking the tyrosine kinase ZAP-70 are unable to up-regulate Fast and undergo AICD, Transfection of wild-type ZAP-70 into the ZAP-7 0-deficient T cells restores their sensitivity to TCR-induced apoptosi s, whereas transfection of catalytically inactive ZAP-70 does not, The se results provide clear evidence that ZAP-70 tyrosine kinase is essen tial in up-regulating Fast for TCR-induced apoptosis.