JNK, BUT NOT MAPK, ACTIVATION IS ASSOCIATED WITH FAS-MEDIATED APOPTOSIS IN HUMAN T-CELLS

Fas is a cell surface molecule that is expressed on a wide array of ce ll types and triggers apoptosis. While in most situations Fas ligation activates programmed cell death, on resting T lymphocytes it can co-s timulate proliferation with the T cell receptor (TCR)/CD3 complex. Thi s incongruity suggests that Fas may elicit signaling events that overl ap with those used by proliferation cues. We observe that in the human T cell line Jurkat and in human peripheral blood lymphocytes. Fas sti mulation does not signal by the Ras/Raf-1/mitogen-activated protein ki nase (MAPK) pathway or by increased intracellular calcium. Rather, Fas ligation strongly activates Jun kinase (JNK). This activity, as well as Fas-induced apoptosis, is blocked by increased levels of cAMP. The balance between proliferation and apoptosis by Fas triggering of T lym phocytes may therefore reflect a signaling ratio between TCR activatio n of the Ras/Raf-1/MAPK pathway versus JNK activation by Fas.