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Modulation of type α transforming growth factor receptors by a phorbol ester tumor promoter
Author(s) -
Davis Roger,
Like Betsy,
Massagué Joan
Publication year - 1985
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240270104
Subject(s) - a431 cells , phosphoserine , epidermal growth factor , receptor , phorbol , biology , phosphorylation , cell surface receptor , epidermoid carcinoma , growth factor , microbiology and biotechnology , chemistry , cell , biochemistry , protein kinase c , cell cycle , serine , oncogene , carcinoma , genetics
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°C induces a complete loss of high‐affinity (K d = 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 α transforming growth factors, eTGF and EGF.