Suppression by staurosporine of Ca2+-mobilization triggered by ligation of antigen-specific receptors on T and B lymphocytes An essential role of protein tyrosine kinase in the signal transduction

AbstractIt is known that the receptor for platelet-derived growth factor (PDGF) activates phospholipase C (PLC) by phosphorylating the γl isoform of PLC with the receptor protein-tyrosine kinase (PTK), whereas a guanine nucleotide-binding protein participates as a transducer in the PLC activation through the receptors for vasopressin, bombesin and prostaglandin F2α (PGF2α). We have shown in a rat fibroblast line that staurosporine is a potent PTK inhibitor capable of clearly discriminating the two types of receptor-stimulated Ca2+ mobilization and, by inference, PLC activation: the response triggered by PDGF was completely inhibited, whereas the responses triggered by vasopressin, bombesin and PGF2α were not affected at all. The Ca2+ mobilization in human T and B cell lines induced by anti-CD3 and anti-immunoglobulins (Ig) was completely suppressed by staurosporine. The results indicate that the PTK activity plays an essential role in the PLC activation through the T cell receptor/CD3 complex and through membrane Ig