Evidence for protein tyrosine kinase involvement in ligand-induced TCR/CD3 internalization and surface redistribution.

摘要: Triggering of the TCR/CD3 complex can lead to its internalization and modulation from cell surface. In present study, we address question dependence on protein tyrosine kinase (PTK) activation. With use an activating anti-clonotypic (anti-Ti) mAb a CTL clone, have shown that PTK inhibitors genistein tyrphostin 25 delayed anti-Ti-induced internalization, but did not affect fluid phase uptake or transferrin receptor cycling. Confocal microscopy with fluorescent anti-Ti revealed inhibition TCR corresponded induction large patches were localized in membrane areas depleted polymerized actin, formation which was dependent combined action inhibitors. contrast effect these inhibitors, depletion Src-like PTKs by T pretreatment herbimycin A led increased rate internalization. Internalization induced monovalent Fab fraction similarly affected although extent less approximately one-half. An analysis substrates phosphorylated assays immunoprecipitates CTL, activated both absence presence genistein, identified bands phosphorylation association CD3 inhibited genistein. Thus, genistein-sensitive activity seems control ligand-induced redistribution