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Accumulation of Epidermal Growth Factor Receptors in Retinoic Acid-Treated Fetal Rat Lung Cells is Due to Enhanced Receptor Synthesis

Departments of Biochemistry and Medicine, Vanderbilt University School of Medicine Nashville, Tennessee, 37232
Department of Anatomy, Loma Linda University School of Medicine Loma Linda, California, 92350

Address requests for reprints to: Graham Carpenter, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.

Abstract

¹²⁵I-Epidermal growth factor (EGF) binding capacity in fetal rat lung (FRL) cells is increased approximately 2 to 3-fold within 18 h of retinoic acid addition. Analysis of ¹²⁵I-EGF binding assays at 0 C reveals approximately 25,000 receptors per cell, while analysis of growth factor binding to retinoic acid-treated cells demonstrates an increase in receptor levels to approximately 70,000 receptors per cell with no detectable changes in receptor affinities.

We show by immunoprecipitation of ³⁵S-methionine labeled EGF receptors that retinoic acid addition produces an increase in the accumulation of EGF receptor protein. Using brief pulses of ³⁵S-methionine, an increase in EGF receptor synthesis can be identified within 3 h after retinoic acid addition. These results are the first to demonstrate that a retinoic acid-induced increase in ¹²⁵I-EGF binding capacity is due to increased EGF receptor protein synthesis. Also, we find that a transient decrease in the rate of EGF receptor turnover occurs when retinoic acid is initially added to FRL cells. On the basis of our data, we conclude that the retinoic acidinduced accumulation of EGF receptors in FRL cells is primarily due to increased receptor synthesis. The effect of retinoic acid on EGF receptor turnover may be a secondary factor, influencing the rate at which receptors accumulate

FOOTNOTES

This research was supported by Grants HL-14214 and CA-24071 from the NIH. A preliminary account of this work was presented at the 72nd Annual Meeting of the Federation of American Societies for Experimental Biology, May 3, 1988.

Received for publication May 24, 1988. Accepted for publication June 22, 1988.

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