Impaired Fas Response and Autoimmunity inPten+/−Mice
| Autor: | Keith B. Elkon, Carlos Cordon-Cardo, Yu Feng Peng, Paraskevi Kotsi, Pier Paolo Pandolfi, Antonio Di Cristofano |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Heterozygote Programmed cell death Tumor suppressor gene T-Lymphocytes Kidney Glomerulus Apoptosis Protein Serine-Threonine Kinases Lymphocyte Activation medicine.disease_cause Autoimmune Diseases Autoimmunity Mice Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins medicine Animals PTEN fas Receptor Phosphorylation PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Autoimmune disease B-Lymphocytes Multidisciplinary biology Tumor Suppressor Proteins PTEN Phosphohydrolase medicine.disease Phosphoric Monoester Hydrolases Mice Inbred C57BL Antibodies Antinuclear Immunoglobulin G Cancer research biology.protein Female Kidney Diseases Signal transduction Proto-Oncogene Proteins c-akt |
| Zdroj: | Science. 285:2122-2125 |
| ISSN: | 1095-9203 0036-8075 |
| DOI: | 10.1126/science.285.5436.2122 |
| Popis: | Inactivating mutations in thePTENtumor suppressor gene, encoding a phosphatase, occur in three related human autosomal dominant disorders characterized by tumor susceptibility. Here it is shown thatPtenheterozygous (Pten+/−) mutants develop a lethal polyclonal autoimmune disorder with features reminiscent of those observed in Fas-deficient mutants. Fas-mediated apoptosis was impaired inPten+/−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 thatPtenis 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|