Modulation of type alpha transforming growth factor receptors by a phorbol ester tumor promoter.
Epidermal growth factor (EGF) and an EGF-like transforming growth factor (eTGF) from retrovirally transformed cells bind to a common receptor type in A431 cells. We have investigated the effects of the tumor promoter phorbol myristate acetate [PMA] on EGF/eTGF receptors in intact A431 cells. Treatment with PMA at 37 degrees C induces a complete loss of high-affinity (Kd = 35-50 pM) binding sites for eTGF and EGF on the cell surface of A431 cells. This effect is half-maximal at 0.1 nM PMA, exhibits rapid kinetics, and persists for at least 4 hr in the presence of PMA. eTGF and PMA added to intact A431 cells induce the phosphorylation of immunoprecipitable 170kd EGF/eTGF receptors. The EGF/eTGF receptor isolated from control cells was found to contain phosphoserine and phosphothreonine. PMA and eTGF caused a marked increase in the level of these two phosphoamino acids. In addition, eTGF but not PMA caused the appearance of phosphotyrosine in the EGF/eTGF receptor in vivo. We conclude that the tumor-promoting phorbol diester regulates both the affinity and phosphorylation state of the A431 cell receptor for the type alpha transforming growth factors, eTGF and EGF.
Davis
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Massagué
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D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000502:physiology*; D066246:ErbB Receptors; D010455:Peptides / Q000378:metabolism / Q000502:physiology*; D010704:Phorbols / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D005253:Sarcoma Viruses, Feline; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015291:Transforming Growth Factors
D010455:Peptides; D010704:Phorbols; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D066246:ErbB Receptors; D013755:Tetradecanoylphorbol Acetate