Transforming growth factor-beta controls receptor levels for epidermal growth factor in NRK fibroblasts.
NRK fibroblasts exposed to transforming growth factor-beta (TGF-beta) show increased binding of radiolabeled epidermal growth factor (EGF) relative to untreated cells. The binding of another growth factor, rat insulin-like growth factor-II, is unaffected. The increase in EGF binding induced by TGF-beta is not due to inhibition of EGF processing nor to an alteration in the affinity of plasma membrane EGF receptors. However, treatment of the cells with TGF-beta does cause a rapid increase in the number of plasma membrane receptors for EGF. TGF-beta has little effect on the rate of overall protein synthesis, but the increase it induces in EGF binding can be completely inhibited by cycloheximide and tunicamycin. Thus a selective synthetic mechanism underlies TGF-beta action. Cells incubated with TGF-beta also show altered down regulation of their EGF receptors in response to the ligand; concentrations of EGF that can induce strong biological responses no longer decrease the plasma membrane receptor level below the basal state. These results agree well with the known specificity and synergism of the interaction between TGF-beta and EGF. Moreover, they describe a mechanism of growth control in which bioactive peptides act coordinately through a regulatory effect on the number of cell-surface receptors.
D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors; D006133:Growth Substances / Q000494:pharmacology*; D007700:Kinetics; D010455:Peptides / Q000494:pharmacology*; D014176:Protein Biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D015291:Transforming Growth Factors; D014415:Tunicamycin / Q000494:pharmacology
D006133:Growth Substances; D010455:Peptides; D011956:Receptors, Cell Surface; D014415:Tunicamycin; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D003513:Cycloheximide; D066246:ErbB Receptors