INDUCTION OF CELL-DEATH VIA FAS (CD95, APO-1) MAY BE ASSOCIATED WITH BUT IS NOT DEPENDENT ON FAS-INDUCED TYROSINE PHOSPHORYLATION

Cross-linking of the Fas-antigen (CD95, Apo-1) triggers apoptosis in a ctivated T cells and transformed T cell lines. Fas-induced apoptosis h as been previously reported to require Fas-triggered tyrosine phosphor ylation of various proteins. In the present study, we have compared th e protein tyrosine phosphorylation pattern and the apoptosis sensitivi ty in a set of Jurkat variants selected for the absence or presence of T cell receptor (TCR)/CD3 expression and resistance or sensitivity to Fas-mediated apoptosis. While tyrosine phosphorylation upon Fas-ligat ion was readily apparent in wild-type Jurkat cells (which are sensitiv e to anti-Fas-induced apoptosis), drastically reduced tyrosine phospho rylation was observed in Fas-resistant Jurkat subclones (which still e xpress CD95 on their surface). More importantly, TCR/CD3-negative Jurk at variants which expressed normal levels of CD95 and were fully susce ptible to Fas-triggered cell death, did not show any protein tyrosine phosphorylation upon Fas-ligation. Taken together, our data demonstrat e that Fas-induced cell death can be associated with but is not depend ent on protein tyrosine phosphorylation.