title: Inhibition of epidermal growth factor receptor biosynthesis caused by the src oncogene product, pp60v-src.
abstract: We have previously shown that an intracellular mechanism down regulates epidermal growth factor (EGF) receptor levels in rodent fibroblasts transformed by the src oncogene (W. J. Wasilenko, L. K. Shawver, and M. J. Weber, J. Cell. Physiol. 131:450-457, 1987). We now report that this down regulation is due to an inhibition of EGF receptor biosynthesis. With Rat-1 (R1) cells infected with a temperature-sensitive src mutant, we found that 125I-labeled EGF binding to cells began to decrease soon after the activation of pp60v-src by shift down to the permissive temperature for transformation. This effect of src on EGF receptors was reversible. Pulse-chase studies with [35S]methionine-labeled cells revealed that the tyrosine protein kinase activity of pp60v-src had little if any effect on EGF receptor degradation rate. By contrast, the expression of pp60v-src caused a large reduction in the apparent rate of EGF receptor biosynthesis. Northern (RNA) blot analysis demonstrated that pp60v-src also caused marked reductions in the steady-state level of EGF receptor mRNA. These data indicate that one way the expression of the src oncogene can affect the machinery of growth control is by affecting the expression of specific genes for growth factor receptors.
authors.affiliation: Department of Microbiology and Cancer Center, University of Virginia Health Sciences Center, Charlottesville 22908.
authors.forename: W J
authors.initials: WJ
authors.lastname: Wasilenko
authors.forename: M
authors.initials: M
authors.lastname: Nori
authors.forename: N
authors.initials: N
authors.lastname: Testerman
authors.forename: M J
authors.initials: MJ
authors.lastname: Weber
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src) / Q000502:physiology*; D051381:Rats; D013696:Temperature; D014170:Transformation, Genetic
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D015688:Oncogene Protein pp60(v-src)