scholarly journals Transcriptional Down-regulation of Epidermal Growth Factor Receptors by Nerve Growth Factor Treatment of PC12 Cells

1998 ◽  
Vol 273 (12) ◽  
pp. 6878-6884 ◽  
Author(s):  
Makoto Shibutani ◽  
Philip Lazarovici ◽  
Alfred C. Johnson ◽  
Yasuhiro Katagiri ◽  
Gordon Guroff
1998 ◽  
Vol 273 (35) ◽  
pp. 22165-22168 ◽  
Author(s):  
Edward M. Mills ◽  
Kazuyo Takeda ◽  
Zu-Xi Yu ◽  
Victor Ferrans ◽  
Yasuhiro Katagiri ◽  
...  

1987 ◽  
Vol 104 (6) ◽  
pp. 1611-1621 ◽  
Author(s):  
P Lazarovici ◽  
G Dickens ◽  
H Kuzuya ◽  
G Guroff

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.


2014 ◽  
Vol 54 (3) ◽  
pp. 574-585 ◽  
Author(s):  
Gadi Cohen ◽  
Keren Ettinger ◽  
Shimon Lecht ◽  
Peter I. Lelkes ◽  
Philip Lazarovici

1983 ◽  
Vol 97 (1) ◽  
pp. 92-98 ◽  
Author(s):  
J Boonstra ◽  
W H Moolenaar ◽  
P H Harrison ◽  
P Moed ◽  
P T van der Saag ◽  
...  

Rat pheochromocytoma cells (clone PC12) respond to nerve growth factor (NGF) by the acquirement of a phenotype resembling neuronal cells. In an earlier study we showed that NGF causes an increase in Na+,K+ pump activity, as monitored by ouabain-sensitive Rb+ influx. Here we show that addition of epidermal growth factor (EGF) to PC12 cells resulted in a stimulation of Na+,K+ pump activity as well. The increase of Na+,K+ pump activity by NGF or EGF was due to increased Na+ influx. This increased Na+ influx was sensitive to amiloride, an inhibitor of Na+,H+ exchange. Furthermore, no changes in membrane potential were observed upon addition of NGF or EGF. Amiloride-sensitive Na+,H+ exchange in PC12 cells was demonstrated by H+ efflux measurements and the effects of weak acids on Na+ influx. These observations suggest that both NGF and EGF activate an amiloride-sensitive, electroneutral Na+,H+ exchange mechanism in PC12 cells. These findings were surprising in view of the opposite ultimate biological effects of NGF and EGF, e.g., growth arrest vs. growth stimulation. However, within 24 h after addition, NGF was found to stimulate growth of PC12 cells, comparable to EGF. In the presence of amiloride, this stimulated growth by NGF and EGF was abolished. In contrast, amiloride did not affect NGF-induced neurite outgrowth of PC12 cells. From these observations it is concluded that in PC12 cells: (a) NGF has an initial growth stimulating effect; (b) neurite outgrowth is independent of increased amiloride-sensitive Na+ influx; and (c) growth stimulation by NGF and EGF is associated with increased amiloride-sensitive Na+ influx.


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