Exp Mol Med.  2001 Dec;33(4):303-309.

D60-sensitive tyrosine phosphorylation is involved in Fas-mediated phospholipase D activation

• Kim JG
• Shin IC
• Lee KS
• Han JS

Abstract

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.

Keyword

Fas; phospholipase D; D609; phosphatidylcholine-specific phospholipase C; tyrosine phosphorylation; protein kinase C; A20 murine cells; genistein

MeSH Terms

Animal
Antibodies, Monoclonal/immunology/*pharmacology
Antigens, CD95/immunology/*metabolism
Bridged Compounds/*pharmacology
Cell Line
Cross-Linking Reagents
Dose-Response Relationship, Immunologic
Enzyme Activation
Genistein/pharmacology
Hydrolysis
Lymphoma/pathology
Mice
Phospholipase C/*antagonists & inhibitors
Phospholipase D/*metabolism
Phosphorylation
Phosphorylcholine/metabolism
Solubility
Thiones/*pharmacology
Tumor Cells, Cultured
Tyrosine/*metabolism
Water/chemistry