CELLULAR-STIMULATION VIA CD95 INVOLVES ACTIVATION OF PHOSPHO-INOSITIDE-3-KINASE

Citation
E. Gulbins et al., CELLULAR-STIMULATION VIA CD95 INVOLVES ACTIVATION OF PHOSPHO-INOSITIDE-3-KINASE, Pflugers Archiv, 435(4), 1998, pp. 546-554
Citations number
54
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
Journal title
ISSN journal
0031-6768
Volume
435
Issue
4
Year of publication
1998
Pages
546 - 554
Database
ISI
SICI code
0031-6768(1998)435:4<546:CVCIAO>2.0.ZU;2-P
Abstract
Several distinct intracellular pathways have been recently shown to be activated during CD95/Fas/APO-1-mediated apoptosis. Here, we demonstr ate that CD95 ligation induces a rapid and transient tyrosine phosphor ylation and activation of phosphoinositide-3-kinase (PI-3-K) in Jurkat T lymphocytes or CD95-sensitive glioma cells. Experiments using p561c k-deficient or p561ck-reconstituted Jurkat clones and the tyrosine kin ase inhibitor herbimycin A revealed that tyrosine phosphorylation and activation of PI-3-K by CD95 depends on expression of Src-like tyrosin e kinases, in particular p561ck. PI-3-K stimulation seems to be critic al for CD95 receptor signalling since, first, inhibition of PI-3-K pre vents CD95-mediated apoptosis and, second, CD95 receptor ligation fail s to induce tyrosine phosphorylation or activation of PI-3-K in CD95-r esistant glioma cells. Thus, PI-3-K activation may be an early signall ing event during CD95-induced apoptosis, and failure to stimulate PI-3 -K may predict tumor cell resistance to CD95-triggered apoptosis.