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

Jong Gon Kim,Joong-Soo Han,Ki Sung Lee,Incheol Shin

doi:10.1038/emm.2001.49

Jong Gon Kim, Joong-Soo Han + Show 2 more

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https://doi.org/10.1038/emm.2001.49

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Journal: Experimental and Molecular Medicine	Publication Date: Dec 1, 2001
Citations: 13	License type: cc-by

Affiliation: Hanyang University

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.

Highlights

Fas known to elicit various signal transduction pathways within animal cells is ubiquitously expressed in lymphoid and nonlymphoid tissues and in many primary tumors and tumor cell lines (Wananabe-Fukunaga et al, 1992; Leithauser et al, 1993; French et al, 1996)
Our studies showed that in vitro phospholipase D (PLD) activity measured by using exogenous substrate in apoptotic Jurkat cell lysates was higher than that of the lysates from untreated control cells, and increased PLD activity during apoptosis was attributed to the PLD of unsaturated fatty acid dependent type
D609-sensitive activation of phosphatidylcholine-specific phospholipase C (PC-PLC) and subsequent activation of protein kinase C (PKC) βI and βII are thought to be responsible for Fas-induced activation of PLD in A20 cells

Summary

Introduction

Fas known to elicit various signal transduction pathways within animal cells is ubiquitously expressed in lymphoid and nonlymphoid tissues and in many primary tumors and tumor cell lines (Wananabe-Fukunaga et al, 1992; Leithauser et al, 1993; French et al, 1996). In A20 murine B lymphoma cell lines, the activation of PC-PLC by Fas ligation elicits activation of protein kinase C (PKC) and phospholipase D (PLD) (Han et al, 1999).

Results

Conclusion