The linker for activation of T cells (LAT) is a transmembrane scaffolding protein that becomes tyrosine phospohorylated after T cell antigen receptor (TCR) engagement, but the role of LAT in T cell activation has been unclear. In 14 June Science, Connie Sommers and colleagues at National Institutes of Health, Bethesda, US, show that blocking signaling through LAT by a single tyrosine mutation inhibits T cell development but induces lymphoproliferation at a later stage.

Sommers et al. used mice having a single tyrosine mutation in LAT and observed that these animals exhibited an early block in T cell maturation but latter developed a polyclonal lymphoproliferative disorder and signs of autoimmune disease. Biochemical analysis of signaling responses showed that in LAT mutant mice the TCR induced activation of phospholipase C-γ1 (PLC- γ1), nuclear factor of activated T cells, calcium influx, interleukin-2 production and cell death were all reduced or...

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