ARF-GEP100, a guanine nucleotide-exchange protein for ADP-ribosylation factor 6, involved in the apoptotic cell death of phagocytes

• Someya Akimasa

  Department of Host Defence and Biochemical Ressearch, Juntendo University, School of Medicine

• Moss Joel

  Pulmonary-Critical Care Medicine Branch, NHLBI, NIH

• Vaughan Martha

  Pulmonary-Critical Care Medicine Branch, NHLBI, NIH

• Nagaoka Isao

  Department of Host Defence and Biochemical Ressearch, Juntendo University, School of Medicine

Bibliographic Information

Other Title

• グアニンヌクレオチド交換タンパク質(guanine nucleotide-exchange protein; GEP)によるマクロファージ様細胞のアポトーシス誘導

Abstract

ADP-ribosylation factors(ARFs) are 20-kDa GTP-binding proteins involved in the vesicular trafficking, the activation of phospholipase D and phosphatidylinositol 4-phosphate 5-kinase, and the modulation of phagocyte functions. Like other GTP-binding proteins, ARFs cycle between GTP-bound, active and GDP-bound, inactive status. Guanine nucleotide-exchange proteins(GEPs), which catalyze the change of bound GDP for GTP, are necessary for the activation of ARFs. Previously, we found a novel GEP with 100kDa, named ARF-GEP₁₀₀. In this study, we elucidated the role in ARF-GEP₁₀₀ on phagocyte functions by transfection of ARF-GEP₁₀₀.<BR>Overexpression of ARF-GEP₁₀₀ induced apoptosis of mouse macrophage RAW264.7 cells and phorbol 12- myristate 13-acetate treated human monocyte U937 cells, which could be detected by morphological changes (nuclear condensation and formation of apoptotic bodies), annexin V-staining and TUNEL assay. ARF-GEP₁₀₀- induced apoptosis was not inhibited by a caspase inhibitor zVAD-FMK. Furthermore, mutant analysis of ARFGEP₁₀₀ revealed that two regions (N- and C- termini) of ARF-GEP₁₀₀ were essential for the induction of apoptosis, but the mutant defective in GDP-GTP exchange domain induced apoptosis. These results suggest that ARFGEP₁₀₀ induces apoptosis of monocytic phagocytes independent of both the caspase activation and GDP-GTP exchange activity.

Journal

• Inflammation and Regeneration

  Inflammation and Regeneration 26 (2), 107-112, 2006

  The Japanese Society of Inflammation and Regeneration

Keywords

• guanine nucleotide-exchange protein
• ARF-GEP
• apoptosis
• phagocyte

Details

• CRID: 1390001205257340672
• NII Article ID: 130004482161
• NII Article ID: 10018657022
• NII Book ID: AA11508953
• DOI: 10.2492/inflammregen.26.107
• ISSN: 18808190
• ISSN: 18809693
• Web Site: https://search.jamas.or.jp/link/ui/2006237762
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed