A LAT mutation that inhibits T cell development yet induces lymphoproliferation |
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Authors: | Sommers Connie L Park Cheung-Seog Lee Jan Feng Chiguang Fuller Claudette L Grinberg Alexander Hildebrand Jay A Lacaná Emanuela Menon Rashmi K Shores Elizabeth W Samelson Lawrence E Love Paul E |
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Institution: | Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. |
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Abstract: | Mice homozygous for a single tyrosine mutation in LAT (linker for activation of T cells) exhibited an early block in T cell maturation but later developed a polyclonal lymphoproliferative disorder and signs of autoimmune disease. T cell antigen receptor (TCR)-induced activation of phospholipase C-gamma1 (PLC-gamma1) and of nuclear factor of activated T cells, calcium influx, interleukin-2 production, and cell death were reduced or abrogated in T cells from LAT mutant mice. In contrast, TCR-induced Erk activation was intact. These results identify a critical role for integrated PLC-gamma1 and Ras-Erk signaling through LAT in T cell development and homeostasis. |
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