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Down-Regulation of c-neu Receptors by Nerve Growth Factor in PC12 Cells
Authors:Mari Oshima  Linnea Weiss  William C Dougall  Mark I Greene  Gordon Guroff
Institution:Section on Growth Factors, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland;and; Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A.
Abstract:Abstract: A small number of p185c- neu receptors have been found on PC12 cells. These receptors show some basal phosphorylation in quiescent cells. When the cells are treated with nerve growth factor (NGF) for a short time, some increase in phosphorylation is seen, mainly on serine and threonine residues, and this is accompanied by a slight shift in the apparent molecular weight. Epidermal growth factor (EGF) also increases the phosphorylation of p185c- neu , in this case on tyrosine residues. Neither heregulin-β1 nor gp30 stimulates the tyrosine phosphorylation of p185c- neu , and neither has a proliferative effect on the cells. Treatment of the cells with NGF for 5 days produces a 70–80% reduction in the number of p185c- neu receptors. This down-regulation does not occur when PC12nnr5 cells, which lack the high-affinity NGF receptor, p140 trk , are treated with NGF.The level of p185c- neu mRNA is not altered by NGF treatment, suggesting that the down-regulation is due to either a translational or a posttranslational alteration.
Keywords:PC12 cells  Nerve growth factor              erbB2 receptor              neu receptor
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