Receptor-mediated effects on ligand availability influence relative mitogenic potencies of epidermal growth factor and transforming growth factor alpha

Journal of Cellular Physiology
C C ReddyD A Lauffenburger

Abstract

Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) elicit quantitatively different cell proliferation responses even though they act via a common receptor, the epidermal growth factor receptor (EGFR). We hypothesized that differential cellular trafficking of available ligand is responsible for the different mitogenic responses elicited by EGF and TGF alpha. Mitogenesis and ligand depletion were determined simultaneously in NR6 mouse fibroblasts expressing either wild-type (WT) or internalization-deficient cytoplasmic domain-truncated (c'973) EGFR. Thus we could determine the effects of both ligand-induced and low level constitutive ligand/receptor processing. For a given initial amount of growth factor, TGF alpha is a weaker stimulus than EGF in cells expressing either form of the EGFR. This difference in the mitogenic potencies correlates with increased depletion of TGF alpha observed during the growth assays. When this difference in ligand depletion is accounted for, or minimized, EGF and TGF alpha elicit quantitatively similar growth responses. Therefore, the relative mitogenic potencies of EGF and TGF alpha depend on ligand availability, as determined by the cellular trafficking of these ligands ...Continue Reading

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Citations

Jul 13, 2002·Journal of Cellular Physiology·Kevin E H LuiSuzanne M Bernier
Apr 13, 1999·Medical & Biological Engineering & Computing·C C ReddyD A Lauffenburger
Nov 10, 2000·Advanced Drug Delivery Reviews·C Uherek, W Wels
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Feb 19, 2009·Molecular and Cellular Biology·David C ClarkeXuedong Liu
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