Biphasic effects of type beta transforming growth factor on epidermal growth factor receptors in NRK fibroblasts. Functional consequences for epidermal growth factor-stimulated mitosis.
Exposure of confluent NRK cells to transforming growth factor-beta (TGF-beta) results in distinct alterations in subpopulations of plasma membrane epidermal growth factor (EGF) receptors. The low affinity sites increase in number, whereas the high affinity sites undergo a transient decrease in affinity followed by a prolonged increase in number. Cycloheximide inhibits both of these effects. Functional assays measuring EGF-stimulated thymidine incorporation in the presence of TGF-beta show that the resulting long-term stimulation of EGF receptor binding is associated with an increased sensitivity to EGF. Similarly, the initial, transient decrease in EGF binding is associated with a temporary inhibition of EGF-stimulated thymidine incorporation. The results describe a bifunctional effect of TGF-beta at the biochemical level consistent with the action of this peptide on NRK cell growth.
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D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D007668:Kidney / Q000166:cytology* / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D015291:Transforming Growth Factors
D010455:Peptides; D011956:Receptors, Cell Surface; D015291:Transforming Growth Factors; D066246:ErbB Receptors; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine