論文

査読有り
2004年11月

Short-term delay of Fas-stimulated apoptosis by GM-CSF as a result of temporary suppression of FADD recruitment in neutrophils: evidence implicating phosphatidylinositol 3-kinase and MEK1-ERK1/2 pathways downstream of classical protein kinase C

JOURNAL OF LEUKOCYTE BIOLOGY
  • Y Kotone-Miyahara
  • ,
  • K Yamashita
  • ,
  • KK Lee
  • ,
  • S Yonehara
  • ,
  • T Uchiyama
  • ,
  • M Sasada
  • ,
  • A Takahashi

76
5
開始ページ
1047
終了ページ
1056
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1189/jlb.0104048
出版者・発行元
FEDERATION AMER SOC EXP BIOL

Granulocyte/macrophage colony-stimulating factor (GM-CSF) inhibits Fas-induced apoptosis of nentrophils. However, the exact step in the apoptotic pathway blocked by GM-CSF remained unclear. Here, we found that pretreatment of neutrophils with GM-CSF inhibits the recruitment of Fas-associated protein with death domain (FADD) to Fas, abolishing the formation of the death-inducing signaling complex required for Fas-induced apoptosis. Two-dimensional electrophoresis revealed that GM-CSF modifies the ratio of FADD subspecies. These GM-CSF-triggered changes were abrogated, and Fas-induced apoptosis was restored by an inhibitor of classical protein kinase C (PKC), Go6976, and by the combination of a phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294002, and an inhibitor of mitogen-activated protein kinase kinase (MEK)1, PD98059. Go6976 blocked GM-CSF-elicited phosphorylation of Akt/PKB and extracellular signal-regulated kinase (ERK)1/2. These results indicated that GM-CSF suppresses Fas-induced neutrophil apoptosis by inhibiting FADD binding to Fas, through redundant actions of PI-3K and MEK1-ERK1/2 pathways downstream of classical PKC.

Web of Science ® 被引用回数 : 23

リンク情報
DOI
https://doi.org/10.1189/jlb.0104048
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/15328334
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000224867500015&DestApp=WOS_CPL

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