Insulin and epidermal growth factor stimulate phosphorylation of p185HER-2 in the breast carcinoma cell line, BT474.
The product of the HER-2 proto-oncogene, p185HER-2, was found to be amplified approximately 10-fold in the human breast carcinoma cell line, BT474, compared to a cell line, HBL-100, derived from normal breast tissue. To explore the possible role of p185HER-2 in growth of the breast carcinoma cells, we investigated factors that may modulate cell growth and phosphorylation of the HER-2 protein product. Two growth factors, epidermal growth factor (EGF) and insulin, stimulated phosphorylation of the HER-2 protein product. In response to insulin, the phosphoserine and phosphothreonine content in p185HER-2 was transiently enhanced about 6-fold. When EGF was added to BT474 cells there was 2- to 3-fold enhanced phosphorylation of serine and threonine residues in p185HER-2 which was maintained for at least 60 min. Although p185HER-2 has been found to be phosphorylated on tyrosine residues following EGF treatment of several different cell types, we estimate that less than 1% of the protein contained phosphotyrosine in the BT474 cells.
Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health Sciences University, Portland 97201.
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Lin
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Li
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Clinton
D001769:Blood; D001943:Breast Neoplasms / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D019000:Phosphotyrosine; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D007328:Insulin; D010768:Phosphoserine; D010769:Phosphothreonine; D019000:Phosphotyrosine; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D014443:Tyrosine; C000715470:MAS1 protein, human