Inhibition of protein breakdown by epidermal growth factor in IMR90 human fibroblasts and other mammalian cell lines

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Abstract
Epidermal growth factor (EGF) inhibits intracellular protein breakdown in IMR90 human fibroblasts and other cell lines having EGF receptors. Inhibition is achieved within 1 h of exposure to the growth factor and is reversed equally rapidly upon removal of EGF. EGF inhibits protein breakdown and stimulates protein and DNA labeling with similar dependency on concentration. Half-maximal effects for all processes with IMR90 and AG2804 [transformed fibroblast] cell lines occur at 0.2 nM and 0.05 nM EGF respectively. EGF and insulin effects on protein breakdown are additive only when the factors are included at suboptimal concentrations. The apparent Kd for EGF binding in several cell lines is .apprx. 10-fold higher than the concentration needed for half-maximal inhibition of protein breakdown. Down-regulation of EGF receptors in IMR90 cells produced a 60% decrease in the binding of 125I-labeled EGF. This was accompanied by a displacement of the concentration curve for EGF inhibition of protein breakdown by .apprx. 2 orders of magnitude, suggesting that protein breakdown can no longer respond to the down-regulated receptor-growth-factor complex. Phorbol esters decrease the inhibitory effect of EGF, but not of insulin, on protein breakdown in IMR90 cells.