Proteasomes Are Involved in the Constitutive Degradation of Growth Hormone Receptors.
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- TAKAGI Kayoko
- Division of Biochemistry and Immunochemistry, National Institute of Health Sciences
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- SAITO Yoshiro
- Division of Biochemistry and Immunochemistry, National Institute of Health Sciences
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- SAWADA Jun-ichi
- Division of Biochemistry and Immunochemistry, National Institute of Health Sciences
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In the mouse Ba/F3-hGHR cell line, which stably expresses human growth hormone receptors (hGHRs), the hGHRs were rapidly degraded in the absence of the ligand. Human growth hormone-binding protein (hGH-BP), a soluble form of hGHR, was released from Ba/F3-hGHR cells, but the hGH-BP release was less than 1% of total hGHRs in the cells. Therefore, the hGH-BP release does not markedly contribute to hGHR degradation in Ba/F3-hGHR cells. The constitutive degradation of hGHRs was inhibited by the proteasome inhibitors MG-132 and clasto-lactacystin β-lactone, or the vacuolar H+-ATPase inhibitor, bafilomycin A1. hGH-enhanced degradation of hGHRs was also inhibited by MG-132. Moreover, MG-132 inhibited the internalization of hGHRs as assessed by 125I-hGH binding to the cell surfaces. Ubiquitinated hGHRs were detected in the cell lysate and increased by hGH-treatment. Furthermore, MG-132 accumulated the ubiquitinated hGHRs induced by hGH. However, the ratio of ubiquitinated hGHRs to unubiquitinated hGHRs was very small, even with treatment involving both hGH and MG-132. In the hGH-untreated cells, the ubiquitinated hGHRs were weakly detected. However, the ubiquitination of hGHR was not enhanced by MG-132 as a result of immunoblotting. Thus, the ubiquitination of hGHR is unlikely to be involved, at least in the constitutive degradation. Taken together, both the proteasome pathway and endosome/lysosome pathway are involved in the constitutive degradation of hGHRs. Our results also suggest that ubiquitination of the hGHR itself is unlikely to be the trigger of the proteasome-dependent degradation.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 24 (7), 744-748, 2001
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679603875456
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- NII論文ID
- 110003638554
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- NII書誌ID
- AA10885497
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- COI
- 1:CAS:528:DC%2BD3MXkvVaru78%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 5820709
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- PubMed
- 11456111
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可