Stabilized Complexes of Epidermal Growth Factor and Its Receptor on the Cell Surface Stimulate RNA Synthesis but not Mitogenesis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 82; no. 24; pp. 8513 - 8517
• Main Authors: Wakshull, E. M., Wharton, Walker
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.12.1985; National Acad Sciences
• Subjects: Animals; Biological and medical sciences; Cell growth; Cell physiology; Cell surface receptors; Cells; Concanavalin A - pharmacology; DNA; DNA - biosynthesis; Endocytosis - drug effects; Epidermal Growth Factor - physiology; ErbB Receptors; Fundamental and applied biological sciences. Psychology; Hormones; Internalization; Kidney; Lectins; Methylmannosides - pharmacology; Mitosis; Molecular and cellular biology; Radioactive decay; Rats; Receptors; Receptors, Cell Surface - physiology; Responses to growth factors, tumor promotors, other factors; RNA; RNA - biosynthesis; Cell culture; Rat; Rodentia; Molecular interaction; Activation; Complexes; Cell surface; Vertebrata; Mammalia; Epidermal growth factor; RNA synthesis; Animal; Internalization; Mitogen; Mechanism of action; Fibroblast; Biological receptor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.82.24.8513

Treatment of mouse fibroblasts, prelabeled at 4 degrees C with125I-labeled epidermal growth factor (EGF), with the lectin concanavalin A (Con A) stabilized the125I-labeled EGF-receptor complex to dissociation and prevented receptor-mediated endocytosis; after 5 hr at 37 degrees C, approximately 50% of the125I-labeled EGF initially bound at 4 degrees C remained cell associated, compared to less than 15% in control cells. The radioactivity lost from the Con A-treated cells was found as intact hormone in the medium, with almost no hormone degradation evident, whereas in control cells most of the medium radioactivity was in the form of low molecular weight degradation products. The trimolecular complex Con A-EGF-receptor was capable of stimulating RNA synthesis to levels greater than control (untreated) or EGF alone and maintained this stimulation for prolonged periods of time. However, there was no effect of Con A treatment on the stimulation of DNA synthesis induced by EGF prebound at 4 degrees C. Thus, maintaining the EGF-receptor complex at the cell surface allows enhanced stimulation of an acute biological response to EGF (RNA synthesis) but not stimulation of DNA synthesis. These data support the idea that processing subsequent to receptor binding is necessary to produce the mitogenic signal.