A LAT Mutation That Inhibits T Cell Development Yet Induces Lymphoproliferation
2002; American Association for the Advancement of Science; Volume: 296; Issue: 5575 Linguagem: Inglês
10.1126/science.1069066
ISSN1095-9203
AutoresConnie L. Sommers, Cheung‐Seog Park, Jan Lee, Chiguang Feng, Claudette L. Fuller, Alexander Grinberg, Jay A. Hildebrand, Emanuela Lacaná, Rashmi K. Menon, Elizabeth W. Shores, Lawrence E. Samelson, Paul E. Love,
Tópico(s)NF-κB Signaling Pathways
ResumoMice 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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