Suppression by staurosporine of Ca(2+)-mobilization triggered by ligation of antigen-specific receptors on t and B lymphocytes. An essential role of protein tyrosine kinase in the signal transduction.
It is known that the receptor for platelet-derived growth factor (PDGF) activates phospholipase C (PLC) by phosphorylating the gamma 1 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 F2 alpha (PGF2 alpha). 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 activations the response triggered by PDGF was completely inhibited, whereas the responses triggered by vasopressin, bombesin and PGF2 alpha 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.
Yamashita
Y
Y
Department of Biochemistry, Sapporo Medical College, Japan.
Hasegawa-Sasaki
H
H
Sasaki
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D015237:Dinoprost / Q000494:pharmacology; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019311:Staurosporine; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology
D000470:Alkaloids; D007529:Isoflavones; D007546:Isoquinolines; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011948:Receptors, Antigen, T-Cell; D014667:Vasopressins; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D015237:Dinoprost; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D019311:Staurosporine; D001839:Bombesin; D002118:Calcium