The Epidermal Growth Factor Receptor and the Product of the neu Protooncogene are Members of a Receptor Tyrosine Phosphorylation Cascade

The protein product of the neu protooncogene, p185, is a tyrosine kinase with a high degree of sequence homology to the epidermal growth factor (EGF) receptor. Although p185 does not bind EGF, EGF stimulates tyrosine phosphorylation of p185. To determine the mechanism of this interaction we have use...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1990-08, Vol.87 (16), p.6054-6057
Main Authors: Connelly, Patricia A., Stern, David F.
Format: Article
Language:English
Subjects:
Analytical, structural and metabolic biochemistry
Animals
Antibodies
Antibodies, Monoclonal
Biological and medical sciences
Cell Line
Cell lines
Cells
Cellular immunity
Enzymes and enzyme inhibitors
ErbB Receptors - genetics
ErbB Receptors - physiology
Fundamental and applied biological sciences. Psychology
Gels
genes
HeLa cells
HeLa Cells - metabolism
Humans
Hydrolases
Mice
Mutation
neu
Phosphorylation
Plasmids
protein-tyrosine kinase
Protein-Tyrosine Kinases - metabolism
Proto-Oncogene Proteins - physiology
Proto-Oncogenes
Receptor, ErbB-2
Receptors
Transfection
Vaccinia
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Summary:The protein product of the neu protooncogene, p185, is a tyrosine kinase with a high degree of sequence homology to the epidermal growth factor (EGF) receptor. Although p185 does not bind EGF, EGF stimulates tyrosine phosphorylation of p185. To determine the mechanism of this interaction we have used a vaccinia virus/bacteriophage T7-based transient gene expression system to induce production of normal and kinase-deficient forms of p185 in the absence and presence of EGF receptors. Tyrosine phosphorylation of kinase-deficient p185 was observed, but only in the presence of the EGF receptor. These findings strongly support the hypothesis that p185 is a substrate for the EGF receptor tyrosine kinase in a tyrosine kinase cascade.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.87.16.6054