D609-sensitive tyrosine phosphorylation is involved in Fas-induced phospholipase D activation

Abstract

As we have previously reported (Han et al., Arch. Biochem. Biophys. 1999, 367:233-239), both Fas and PMA could activate phospholipase D via activation of protein kinase Cb in A20 cells. To explain the difference in the magnitudes of increase in phospholipase D activity by Fas (approximately 4 fold over control level) and PMA (approximately 2.5 fold), the possible involvement of tyrosine phosphorylation in Fas-induced activation of phospholipase D was tested. In one minute after Fas cross-linking, there was a prominent increase in tyrosine phosphorylated proteins and it was completely inhibited by D609, previously known as a specific inhibitor of phosphatidylcholine-specific phospholipase C. Data also suggested that a tyrosine kinase inhibitor, genistein could partially inhibit Fas-induced phospholipase D activation. There was no effect of genistein on Fas-induced activation of phosphatidylcholine-specific phospholipase C and protein kinase C. We present here the first report that D609-sensitive tyrosine phosphorylation may in part account for the increase in phospholipase D activity by Fas cross-linking.