Down-regulation of c-neu receptors by nerve growth factor in PC12 cells.
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-beta 1 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, p140trk, 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.
Oshima
M
M
Section on Growth Factors, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Weiss
L
L
Dougall
W C
WC
Greene
M I
MI
Guroff
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015536:Down-Regulation; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*
D015335:Molecular Probes; D009414:Nerve Growth Factors; D018719:Erb-b2 Receptor Tyrosine Kinases