p185neu is phosphorylated on tyrosine in human primary breast tumors which overexpress neu/erbB-2.
A series of primary human breast tumors was analysed by immunoblotting with anti-neu antibodies. Overproduction of the neu protein-tyrosine kinase, p185neu, was observed in 23 of 56 malignant tumor samples. 29 of these tumors were also immunoblotted with antiphosphotyrosine antibodies. A single prominent phosphotyrosine-containing protein, which co-migrated with p185neu was identified in 11 of the 29 tumors examined. There was an exact concordance between the tumors with a 185kDa phosphotyrosine-containing protein, and those with elevated p185neu. These results indicate that overexpressed p185neu in primary human breast cancer is phosphorylated on tyrosine, most likely by autophosphorylation, and by inference is enzymatically activated as a protein-tyrosine kinase. Aberrant tyrosine phosphorylation may therefore be important in the development of a substantial fraction of breast cancers.
Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Y
Y
Wildenhain
T
T
Pawson
M E
ME
Blackstein
I L
IL
Andrulis
D000906:Antibodies / Q000276:immunology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D010766:Phosphorylation; D019000:Phosphotyrosine; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D019000:Phosphotyrosine; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D014443:Tyrosine