Impaired Fas Response and Autoimmunity in Pten +/− Mice
- 24 September 1999
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 285 (5436) , 2122-2125
- https://doi.org/10.1126/science.285.5436.2122
Abstract
Inactivating mutations in the PTEN tumor suppressor gene, encoding a phosphatase, occur in three related human autosomal dominant disorders characterized by tumor susceptibility. Here it is shown that Pten heterozygous (Pten +/−) mutants develop a lethal polyclonal autoimmune disorder with features reminiscent of those observed in Fas-deficient mutants. Fas-mediated apoptosis was impaired in Pten +/− mice, and T lymphocytes from these mice show reduced activation-induced cell death and increased proliferation upon activation. Phosphatidylinositol (PI) 3-kinase inhibitors restored Fas responsiveness inPten +/− cells. These results indicate thatPten is an essential mediator of the Fas response and a repressor of autoimmunity and thus implicate the PI 3-kinase/Akt pathway in Fas-mediated apoptosis.Keywords
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