Modulation of a Mr 175,000 c-neu receptor isoform in G8/DHFR cells by serum starvation.
The neu proto-oncogene product has been found to exist in two interconvertible forms in G8/DHFR mouse fibroblasts. The 185-kilodalton form (p185) present in growing cells is replaced by a 175-kilodalton form (p175) under conditions of serum starvation. This low molecular weight form accounts almost exclusively for the phosphotyrosine content of the receptor and is associated with increased tyrosine kinase activity. Addition of serum, platelet-derived growth factor or tumor promoter induces conversion of p175 to p185 within minutes, and this increase in molecular weight is associated with phosphorylation of serine and threonine; removal of serum growth factors is followed by replacement of p185 with p175 over several hours. Unlike G8/DHFR cells, the human breast cancer cell line SK-Br-3 expresses a high molecular weight neu/HER2 receptor with unchanged phosphotyrosine content in both serum-starved and serum-stimulated cultures. These findings indicate that activation of the neu proto-oncogene product in G8/DHFR cells may be regulated in part by protein kinase C-mediated receptor transmodulation rather than by ligand availability alone.
Epstein
R J
RJ
Division of Cell and Molecular Biology, Harvard Medical School, Boston, Massachusetts 02115.
Druker
B J
BJ
Roberts
T M
TM
Stiles
C D
CD
D000818:Animals; D001769:Blood; D002460:Cell Line; D003470:Culture Media; D005347:Fibroblasts / Q000201:enzymology; D015151:Immunoblotting; D051379:Mice; D008970:Molecular Weight; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
D003470:Culture Media; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D013762:Tetrahydrofolate Dehydrogenase; C000715470:MAS1 protein, human