Modulation of type α transforming growth factor receptors by a phorbol ester tumor promoter

✍ Scribed by Roger Davis; Betsy Like; Joan Massagué

• Publisher: John Wiley and Sons
• Year: 1985
• Tongue: English
• Weight: 501 KB
• Volume: 27
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240270104

✦ Synopsis

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 A43 1 cells. Treatment with PMA at 37°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 A43 1 cells induce the phosphorylation of immunoprecipitable 170kd EGF /eTGF receptors. The EGFI 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 a transforming growth factors, eTGF and EGF.