RAPID FLUX IN TRANSFORMING GROWTH-FACTOR-BETA RECEPTORS ON BONE-CELLS

The proportion of transforming growth factor-beta (TGF-beta) binding a mong conventional membrane receptors on bone cells can vary with hormo ne or growth factor treatment or with the state of osteoblast-like act ivity and appears to determine the nature of its biological effects. T herefore, functional TGF-beta receptor stability could be an important aspect of regulation, Suppression of protein synthesis reduced TGF-be ta binding to types I and II receptors with t(1/2) of 2 h and to betag lycan with t(1/2) of 6 h. In contrast, suppression of mRNA transcripti on reduced TGF-beta binding at least 3-fold more slowly at each recept or site, Preexposure to TGF-beta decreased its binding at all three si tes within 4 h in osteoblast-enriched cultures. This effect was transi ent with lower TGF-beta concentrations, where the receptor profile was nearly fully restored within 24-48 h, In contrast, less differentiate d bone cells were less sensitive to ligand-dependent receptor down-reg ulation. Agents that alter protein kinase and phosphatase activity als o modified the TGF-beta binding profile in specific ways, Together, th ese results indicate that cell surface TGF-beta receptors turn over ra pidly by ligand-independent and ligand-dependent mechanisms, demonstra te 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.