D609-sensitive tyrosine phosphorylation is involved in Fas-mediated phospholipase D activation.
Both Fas and PMA can activate phospholipase D via activation of protein kinase Cbeta in A20 cells. Phospholipase D activity was increased 4 fold in the presence of Fas and 2.5 fold in the presence of PMA. The possible involvement of tyrosine phosphorylation in Fas-induced activation of phospholipase D was investigated. In five minute after Fas cross-linking, there was a prominent increase in tyrosine phosphorylated proteins, and it was completely inhibited by D609, a specific inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC). A tyrosine kinase inhibitor, genistein, can partially inhibit Fas-induced phospholipase D activation. There were no effects of genistein on Fas-induced activation of PC-PLC and protein kinase C. These results strongly indicate that tyrosine phosphorylation may in part account for the increase in phospholipase D activity by Fas cross-linking and D609 can block not only PC-PLC activity but also tyrosine phosphorylation involved in Fas-induced phospholipase D activation.
Kim
J G
JG
Institute of Biomedical Sciences and Department of Biochemistry, College of Medicine, Hanyang University, Seoul, Korea.
Shin
I
I
Lee
K S
KS
Han
J S
JS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002460:Cell Line; D003432:Cross-Linking Reagents; D004306:Dose-Response Relationship, Immunologic; D004789:Enzyme Activation; D019833:Genistein / Q000494:pharmacology; D006868:Hydrolysis; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D009636:Norbornanes; D010739:Phospholipase D / Q000378:metabolism*; D010766:Phosphorylation; D010767:Phosphorylcholine / Q000378:metabolism; D012995:Solubility; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*; D014443:Tyrosine / Q000378:metabolism*; D014867:Water / Q000737:chemistry; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D001952:Bridged-Ring Compounds; D003432:Cross-Linking Reagents; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; D019014:fas Receptor; D014867:Water; D010767:Phosphorylcholine; D014443:Tyrosine; C046498:tricyclodecane-9-yl-xanthogenate; D019833:Genistein; D010738:Type C Phospholipases; D010739:Phospholipase D