Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor

Abstract

A novel v-erb-B-related gene, c-erb-B-2, which has been identified in the human genome, maps to human chromosome 17 at q21 (ref. 40), and seems to encode a polypeptide with a kinase domain that is highly homologous with, but distinct from, that of the epidermal growth factor (EGF) receptor. The c-erb-B-2 gene is conserved in vertebrates and it has been suggested that the neu gene, detected in a series of rat neuro/glioblastomas, is, in fact, the rat c-erb-B-2 gene. Amplification of the c-erb-B-2 gene in a salivary adenocarcinoma and a gastric cancer cell line MKN-7 suggests that its over-expression is sometimes involved in the neoplastic process. To determine the nature of the c-erb-B-2 protein, we have now molecularly cloned complementary DNA for c-erb-B-2 messenger RNA prepared from MKN-7 cells. Its sequence shows that the c-erb-B-2 gene encodes a possible receptor protein and allows an analysis of the similarity of the protein to the EGF receptor and the neu product. As a consequence of chromosomal aberration in MKN-7 cells, a 4.6-kilobase (kb) normal transcript and a truncated 2.3-kb transcript of c-erb-B-2 are synthesized at elevated levels. The latter transcript presumably encodes only the extracellular domain of the putative receptor.

Immune responses to all ErbB family receptors detectable in serum of cancer patients

“…Anti-EGFR antiserum E7 (Fedi et al, 1994), anti-ErbB2 antiserum M6 (Alimandi et al, 1995) and antiErbB3 antiserum MK4 (Kraus et al, 1993) were raised in rabbits against synthetic peptides of the respective human coding sequence [EGFR: aa 1172 ± 1186 (Ullrich et al, 1984), ErbB2: aa 1218 ± 1232 (Yamamoto et al, 1986), ErbB3: aa 1191 ± 1205 (Kraus et al, 1989)]. ErbB4 antiserum was generated against a GST-fusion protein with the carboxyl-terminal ErbB4 domain .…”

Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tryosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4

“…These four receptors are widely expressed in epithelial, mesenchymal, and neuronal tissues and have been implicated in the progression of certain types of human cancer as well as in development (Ullrich et al, 1984;Slamon et al, 1987;Plowman et al, 1990;Lai and Lemke, 1991;Lemoine et al, 1992;Prigent et al, 1992;reviewed in Hynes and Stern, 1994). The receptors possess a high degree of sequence homology (40 ± 50%) and have a similar molecular structure consisting of an extracellular ligand binding domain, transmembrane domain, protein tyrosine kinase domain, and a C-terminal autophosphorylation domain (Ullrich et al, 1984;Yamamoto et al, 1986;Kraus et al, 1989;Plowman et al, 1990Plowman et al, , 1993a.…”

The N-terminal common domain of simian virus 40 large T and small t antigens acts as a transformation suppressor of the HER-2/neu oncogene

“…The blotted RNAs were then hybridized at 428C with random-primed 32 Plabeled probes prepared by using Rediprime Random primer labeling kit (Amersham). For the detection of HER-2/neu mRNA, the probes used were two AccI fragments (0.8 and 1.2 kb) isolated from the plasmid pCER204 (Yamamoto et al, 1986). For the detection of GAPDH mRNA, a full-length GAPDH cDNA was used as probe (Fort et al, 1985).…”

“…The blotted DNAs were then hybridized at 428C with a combination of 32 P-labeled human HER-2/neu speci®c probes. The probes were prepared by labeling two AccI fragments (0.8 and 1.2 kb) and one SmaI fragment (0.3 kb) isolated from the plasmid pCER204 (Yamamoto et al, 1986) with 32 P using Rediprime Random primer labeling kit (Amersham). The blots were washed twice at 258C for 30 min with cold wash bu er (26SSC and 0.2% SDS) and once at 558C for 10 min with hot wash bu er (0.16SSC and 0.2% SDS).…”

“…The HER-2/neu (also known as c-erbB-2) protooncogene encodes a molecular weight of 185 kDa epidermal growth factor receptor-related transmembrane protein with intrinsic tyrosine kinase activity (Coussens et al, 1985;Hung et al, 1986;Yamamoto et al, 1986). Ampli®cation or overexpression of HER-2/ neu has been detected frequently in many types of human cancers, including cancers of the breast, ovary, lung, kidney, colon, bladder, esophagus, stomach, mouth and salivary gland (reviewed by Hynes and Stern, 1994).…”