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Impaired Fas response and autoimmunity in Pten+/- mice.
Di Cristofano, A; Kotsi, P; Peng, Y F; Cordon-Cardo, C; Elkon, K B; Pandolfi, P P.
Afiliación
  • Di Cristofano A; Department of Human Genetics-Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.
Science ; 285(5436): 2122-5, 1999 Sep 24.
Article en En | MEDLINE | ID: mdl-10497129
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 in Pten+/- cells. These results indicate that Pten 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.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Proteínas Serina-Treonina Quinasas / Apoptosis / Monoéster Fosfórico Hidrolasas / Receptor fas / Proteínas Supresoras de Tumor / Enfermedades Renales Límite: Animals Idioma: En Revista: Science Año: 1999 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Buscar en Google
Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Autoinmunes / Proteínas Serina-Treonina Quinasas / Apoptosis / Monoéster Fosfórico Hidrolasas / Receptor fas / Proteínas Supresoras de Tumor / Enfermedades Renales Límite: Animals Idioma: En Revista: Science Año: 1999 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos