| Budget Amount *help |
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
Engagement of T cell receptor(TCR)-CD3 complexes on T-cells rapidly provokes tyrosine phosphorylation of cellular proteins, which is thought to be a essential step to the following events of T-cell activation. p56^<lck>, a member of src-related non-receptor type protein tyrosine kinases, is expressed exclusively in T-cells. Accumulating date suggest that p56^<lck> is one of the responsible kinases for TCR-mediated protein tyrosine phosphorylation. To investigate the role of p56^<lck> in TCR signaling in detail, we injected anti-Lck monoclonal antibody (mAb), MOL171 or MOL294, which specifically suppresses Lck kinase activity in vitro, into Jurkat T-cells by erythrocyte-ghost procedure in order to block the activity of p56^<lck>. In Jurkat cells injected with anti-Lck mAb, intracellular Ca^<2+> mobilization induced by TCR stimulation was markedly reduced in comparison with control mouse IgG-injected samples. This reduction of Ca^<2+> influx seems to be specific for TCR-signaling because anti-LcK mAb-injection did not cause significant suppression of phytohaemagglutinin-induced Ca^<2+> increase. Furthermonr, injection of anti-Lck mAb inhibited TCR-mediated protein tyrosine phosphorylation of 100 kDa protein and phoshplipase Cgamma1. These results confirm that p56^<lck> an indispensable of TCR signaling and p100 and phospholipase Cgamma1 are strongly proposed to be candidates for substrates for p56^<lck>.
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