A LAT Mutation That Inhibits T Cell Development Yet Induces Lymphoproliferation
- 14 June 2002
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 296 (5575) , 2040-2043
- https://doi.org/10.1126/science.1069066
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–γ1 (PLC-γ1) 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-γ1 and Ras-Erk signaling through LAT in T cell development and homeostasis.Keywords
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