Signaling via LAT (linker for T-cell activation) and Syk/ZAP70 is requiredfor ERK activation and NFAT transcriptional activation following CD2 stimulation

Activation of T cells can be initiated through cell surface molecules in ad dition to the T-cell receptor-CD3 (TCR-CD3) complex. In human T cells, liga tion of the CD2 molecule by mitogenic pairs of anti-CD2 monoclonal antibodi es activates T cells via biochemical signaling pathways similar but not ide ntical to those elicited on TCR engagement. This study describes a key role for the p36/38 membrane adapter protein linker for T cell activation (LAT) in CD2-mediated T cell activation. Following ligation of CD2 on the surfac e of the Jurkat T-cell line and human purified T cells, LAT was tyrosine ph osphorylated and shown to associate in vivo with a number of other tyrosine phosphorylated proteins including PLC gamma-1, Grb-2, and SLP-76. Using Ju rkat cell lines deficient in ZAP70/Syk (P116) or LAT (ANJ3) expression, CD2 -dependent PLC gamma-1 and SLP-76 tyrosine phosphorylation required express ion both of ZAP70 or Syk and of LAT. As predicted, the absence of either LA T or ZAP70/Syk kinases correlated with a defect in the induction of nuclear factor of activated T cells (NFAT) transcriptional activity, activation of the interleukin-2 promoter, and ERK phosphorylation following CD2 stimulat ion. These data suggest that LAT is an adapter protein important for the re gulation of CD2-mediated T-cell activation. (Blood. 2000;96:2181-2190) (C) 2000 by The American Society of Hematology.