Rapid flux in transforming growth factor-beta receptors on bone cells.
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 t1/2 of 2 h and to betaglycan with t1/2 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.
Centrella
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M
Section of Plastic Surgery, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8041, USA.
Ji
C
C
Casinghino
S
S
McCarthy
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TL
D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D017931:DNA Primers; D008024:Ligands; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases