論文 - 詳細
| RRC ID | 42171 |
|---|---|
| 著者 | Fukushima K, Ishiyama C, Yamashita K. |
| タイトル | Recognition by TNF-alpha of the GPI-anchor glycan induces apoptosis of U937 cells. |
| ジャーナル | Arch Biochem Biophys |
| Abstract |
Tumor necrosis factor-alpha (TNF-alpha) binds to TNF-alpha receptors (TNFR) to produce a hexameric (TNF-alpha)(3)-(TNFR)(3) structure that stimulates apoptosis. We found by using ELISA that TNF-alpha binds to the glycosylphosphatidylinositol (GPI) anchor glycans of carcinoembryonic antigen, human placental alkaline phosphatase (hAP), and Tamm-Horsfall glycoprotein. These binding abilities were inhibited by 10(-6)M mannose-6-phosphate. Treatment of hAP with mild acid and phosphatase, which releases the N-acetylglucosamine (GlcNAc) beta1 -->phosphate-->6 residue from the GPI-anchor glycan of hAP, abrogated the binding of TNF-alpha to hAP. Thus, TNF-alpha binds to the GlcNAcbeta1-->phosphate-->6Man residue in GPI-anchor glycans. To investigate whether the carbohydrate-binding ability of TNF-alpha is related to its physiological functions, human lymphoma U937 cells were used. TNF-alpha stimulates U937 cell apoptosis in a dose-dependent manner and the presence of mannose-6-phosphate inhibited this. TNF-alpha-dependent tyrosine phosphorylation of several proteins in U937 cells was also diminished by mannose-6-phosphate. Phosphatidylinositol-specific phospholipase C-pretreatment also inhibited this tyrosine phosphorylation. These data suggest that TNF-alpha stimulates U937 cell apoptosis by forming a high-affinity nanomeric (TNF-alpha)(3)-(TNFR)(3)-(GPI-anchored glycan)(3) complex. The GPI-anchored glycoprotein involved remains to be identified. |
| 巻・号 | 426(2) |
| ページ | 298-305 |
| 公開日 | 2004-6-15 |
| DOI | 10.1016/j.abb.2004.02.028 |
| PII | S000398610400116X |
| PMID | 15158680 |
| MeSH | Apoptosis / drug effects Apoptosis / physiology* Cell Cycle Proteins / metabolism* Dose-Response Relationship, Drug GPI-Linked Proteins Humans Mannosephosphates / metabolism* Mannosephosphates / pharmacology Membrane Proteins / metabolism* Neoplasm Proteins / metabolism* Protein Binding Signal Transduction / drug effects Signal Transduction / physiology* Tumor Necrosis Factor-alpha / metabolism* Tumor Necrosis Factor-alpha / pharmacology U937 Cells |
| IF | 3.391 |
| 引用数 | 6 |
| WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | U-937 DE-4(RCB0435) |