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| The ubiquitin conjugation system is required for ligand-induced endocytosis and degradation of the growth hormone receptor |
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| Author(s): Strous GJ, vanKerkhof P, Govers R, Ciechanover A, Schwartz AL |
| Source: EMBO JOURNAL Volume: 15 Issue: 15 Pages: 3806-3812 Published: AUG 1 1996 |
| Times Cited: 223 References: 39 |
| Abstract: The ubiquitin-dependent protein degradation system has recently been implicated in downregulation of signal transducing receptors. Growth hormone receptor (GHR) cDNA was transfected into Chinese hamster ovary cells, which exhibit a temperature-sensitive defect in ubiquitin conjugation (CHO-ts20), as well as into wild-type cells (CHO-E36). Upon binding of growth hormone (GH), two GHR polypeptides dimerize and initiate signal transduction. In CHO-E36 and in CHO-ts20 at the permissive temperature the GHR was ubiquitinated and degraded in a GH-dependent fashion. However, at the non-permissive temperature in CHO-ts20 cells, neither GH-dependent uptake nor degradation of the GHR was observed, while in CHO-E36 cells both GHR uptake and degradation were accelerated. Incubation of CHO-E36 cells with inhibitors of endosomal/lysosomal function (NH4Cl, bafilomycin A1) markedly reduced ligand-induced GHR degradation. Our results indicate that a functional ubiquitin conjugating system is required for GH-induced endocytosis and that degradation of both the exoplasmic and cytoplasmic portions of the GHR occurs within the endosomal/lysosomal compartment. |
| Document Type: Article |
| Language: English |
| Reprint Address: Strous, GJ (reprint author), UNIV UTRECHT, FAC MED, DEPT CELL BIOL, HEIDELBERGLAAN 100, NL-3584 CX UTRECHT, NETHERLANDS |
Addresses:
1. UNIV UTRECHT, BIOMEMBRANE INST, NL-3584 CX UTRECHT, NETHERLANDS
2. TECHNION ISRAEL INST TECHNOL, DEPT BIOCHEM, FAC MED, IL-31096 HAIFA, ISRAEL
3. WASHINGTON UNIV, DEPT BIOL MOL, ST LOUIS, MO 63110 USA
4. WASHINGTON UNIV, DEPT PEDIAT & PHARMACOL, ST LOUIS, MO 63110 USA |
| Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: VC667 |
| ISSN: 0261-4189 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |