The Product of the Human c- erb B-2 Gene: a 185-Kilodalton Glycoprotein with Tyrosine Kinase Activity

Abstract

Antibodies were raised against a synthetic peptide corresponding to 14 amino acid residues at the COOH-terminus of a protein deduced from the human c-erbB-2 nucleotide sequence. These antibodies immunoprecipitated a 185-kilodalton glycoprotein from MKN-7 adenocarcinoma cells. Incubation of the immunoprecipitates with (gamma-32P)ATP resulted in the phosphorylation of this protein on tyrosine residues. These results indicate that the human c-erbB-2 gene product is the 185-kilodalton glycoprotein that is associated with tyrosine kinase activity. Although the c-erbB-2 protein was predicted to encode a protein very similar to epidermal growth factor (EGF) receptor, EGF did not stimulate this kinase activity either in vivo or in vitro.

Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells

“…EGFR is activated upon binding to its ligands, such as epidermal growth factor (EGF) and TGF-a (Pawson, 1995;Schlessinger and Ullrich, 1992). There is no known ligand for ErbB2, but its activation is believed to be due to its overexpression (Akiyama et al, 1986;DiGiovanna and Stern, 1995). Upon activation, either by ligand binding or protein overexpression, dimerization and stabilization of RTKs occur, resulting in stimulation of tyrosine kinase activities and autophosphorylation on tyrosine residues (Downward et al, 1984;Hazan et al, 1989;Margolis et al, 1989).…”

Rat Muc4 (sialomucin complex) reduces binding of anti‐ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance

“…[1][2][3][4][5] Through its heterodimerization with other ErbB receptors, ErbB2 can mediate signal transduction from all ErbB receptors and thus be involved in a variety of cell functions, including cell proliferation, differentiation and apoptosis. 6 -8 ErbB2 also plays a role in human malignancies.…”

Correlation between encoded protein overexpression and copy number of the HER2 gene with survival in non‐small cell lung cancer

“…The product of the HER2 (erbB2) gene is a 185 dalton transmembrane protein (p185 HER2 ) tyrosine kinase. 7 In human cancers, the gene is overexpressed by amplification rather than mutated to constitutively activate cancer cell proliferation. For instance, amplification of the HER2 gene has been reported in several types of cancer, including breast, ovarian and stomach, 8,9 and most of these cases have been associated with poor prognosis.…”