The role of Lck in TCR-CD4 receptor signaling

1992 Fiscal Year Final Research Report Summary

• Project/Area Number: 03454197
• Research Category: Grant-in-Aid for General Scientific Research (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: KYUSHU UNIVERSITY
• Principal Investigator: KOGA Yasuhiro Medical Institute of Bioregulation, Department of Immunology. Associate Professor., 生体防御医学研究所, 助教授 (60170221)
• Project Period (FY): 1991 – 1992
• Keywords: Lck / TCR / Ca^<2+>

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>.