Rapid flux in transforming growth factor-beta receptors on bone cells

被引:45
作者
Centrella, M
Ji, CH
Casinghino, S
McCarthy, TL
机构
[1] Section of Plastic Surgery, School of Medicine, Yale University, New Haven
[2] Section of Plastic Surgery, Yale University, School of Medicine, New Haven, CT 06520-8041
关键词
D O I
10.1074/jbc.271.31.18616
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The proportion of transforming growth factor-beta (TGF-beta) binding among conventional membrane receptors on bone cells can vary with hormone or growth factor treatment or with the state of osteoblast-like activity and appears to determine the nature of its biological effects. Therefore, functional TGF-beta receptor stability could be an important aspect of regulation, Suppression of protein synthesis reduced TGF-beta binding to types I and II receptors with t(1/2) of 2 h and to betaglycan with t(1/2) of 6 h. In contrast, suppression of mRNA transcription reduced TGF-beta binding at least 3-fold more slowly at each receptor site, Preexposure to TGF-beta decreased its binding at all three sites within 4 h in osteoblast-enriched cultures. This effect was transient with lower TGF-beta concentrations, where the receptor profile was nearly fully restored within 24-48 h, In contrast, less differentiated bone cells were less sensitive to ligand-dependent receptor down-regulation. Agents that alter protein kinase and phosphatase activity also modified the TGF-beta binding profile in specific ways, Together, these results indicate that cell surface TGF-beta receptors turn over rapidly by ligand-independent and ligand-dependent mechanisms, demonstrate that the binding capacity of TGF-beta receptors is less stable than their mRNAs, and that functional receptor levels may be determined in part by post-transcriptional events.
引用
收藏
页码:18616 / 18622
页数:7
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