RGD Reference Report - Long-term, heterologous down-regulation of the epidermal growth factor receptor in PC12 cells by nerve growth factor. - Rat Genome Database

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Long-term, heterologous down-regulation of the epidermal growth factor receptor in PC12 cells by nerve growth factor.

Authors: Lazarovici, P  Dickens, G  Kuzuya, H  Guroff, G 
Citation: Lazarovici P, etal., J Cell Biol. 1987 Jun;104(6):1611-21.
RGD ID: 5131535
Pubmed: PMID:3495539   (View Abstract at PubMed)
PMCID: PMC2114511   (View Article at PubMed Central)

Cells of the rat pheochromocytoma clone PC12 possess receptors for both nerve growth factor (NGF) and epidermal growth factor (EGF), thus enabling the study of the interaction of these receptors in the regulation of proliferation and differentiation. Treatment of the cells with NGF induces a progressive and nearly total decrease in the specific binding of EGF beginning after 12 h and completed within 4 d. Three different measures of receptor show that the decreased binding capacity represents, in fact, a decreased amount of receptor: (a) affinity labeling of PC12 cell membranes by cross-linking of receptor-bound 125I-EGF showed a 60-90% decrease in the labeling of 170- and 150-kD receptor bands in cells treated with NGF for 1-4 d; (b) EGF-dependent phosphorylation of a src-related synthetic peptide or EGF receptor autophosphorylation with membranes from NGF-differentiated cells showed a decrease of 80 and 90% in the tyrosine kinase activity for the exogenous substrate and for receptor autophosphorylation, respectively; (c) analysis of 35S-labeled glycoproteins isolated by wheat germ agglutinin-Sepharose chromatography from detergent extracts of PC12 membranes showed a 70-90% decrease in the 170-kD band in NGF-differentiated cells. These findings permit the hypothesis that long-term heterologous down-regulation of EGF receptors by NGF in PC12 cells is mediated by an alteration in EGF receptor synthesis. It is suggested that this heterologous down-regulation is part of the mechanism by which differentiating cells become insensitive to mitogens.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to growth factor stimulus  IEP 5131535nerve growth factorRGD 

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)


Additional Information