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Fas or ceramide induce apoptosis by Ras‐regulated phosphoinositide‐3‐kinase activation
Author(s) -
Gulbins Erich,
Brenner Birgit,
Koppenhoefer Ursula,
Linderkamp Otwin,
Lang Florian
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.63.2.253
Subject(s) - ceramide , biology , apoptosis , microbiology and biotechnology , phosphoinositide 3 kinase , kinase , signal transduction , sphingolipid , cancer research , pi3k/akt/mtor pathway , biochemistry
We demonstrate a rapid and transient activation of phosphoinositide‐3‐kinase (PI‐3‐K) by Fas receptor triggering or cellular treatment with synthetic C6‐ceramide. The stimulation of PI‐3‐K is critical for Fas or C6‐ceramide‐induced programmed cell death because transfection with a transdominant inhibitory PI‐3‐K construct or pretreatment with the PI‐3‐K inhibitor wortmannin almost completely prevented Fas or C6‐ceramide‐mediated apoptosis. Treatment with the caspase inhibitor Ac‐YVAD‐cmk or cellular transfection with transdominant inhibitory N17Ras prevented PI‐3‐K stimulation by Fas, suggesting that Fas activates PI‐3‐K via caspases and Ras. N17Ras expression also prevented C6‐ceramide‐initiated PI‐3‐K stimulation. The notion of a PI‐3‐K regulation by Ras upon Fas receptor ligation or ceramide treatment is supported by co‐immunoprecipitation experiments revealing an activation‐dependent association of PI‐3‐K and Ras. J. Leukoc. Biol . 63: 253–263; 1998.