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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The erbB2 oncogene encodes a 185-kilodalton transmembrane protein whose sequence is similar to the epidermal growth factor receptor (EGFR). A 30-kilodalton factor (gp30) secreted from MDA-MB-231 human breast cancer cells was shown to be a ligand for p185erbB2. An antibody to EGFR abolished the tyrosine phosphorylation induced by EGF and transforming growth factor-alpha (TGF-alpha) but only partially blocked that produced by gp30 in SK-BR-3 breast cancer cells. In two cell lines that overexpress erbB2 but do not expresss EGFR (MDA-MB-453 breast cancer cells and a Chinese hamster ovary cell line that had been transfected with erbB2), phosphorylation of p185erbB2 was induced only by gp30. The gp30 specifically inhibited the growth of cells that overexpressed p185erbB2. An antibody to EGFR had no effect on the inhibition of SK-BR-3 cell colony formation obtained with gp30. Thus, it appeared that gp30 interacted directly with the EGFR and erbB2. Direct binding of gp30 to p185erbB2 was confirmed by binding competition experiments, where gp30 was found to displace the p185erbB2 binding of a specific antibody to p185erbB2. The evidence described here suggests that gp30 is a ligand for p185erbB2.
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PMID:Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2. 221 96

Investigations of the pathways regulating normal growth of epithelial cells have revealed the existence of two major growth-factor signaling cascades required for proliferation. One pathway is activated by IGF-1 or high insulin concentration. The other is triggered by EGF, TGF alpha, or members of the FGF family, including the recently discovered epithelial-cell-specific growth factor, designated keratinocyte growth factor (KGF). Its expression pattern in vivo suggests that KGF plays an important normal physiologic role as a stromal effector of epithelial cell proliferation. Oncogenes, which represent constitutively activated forms of genes critically involved in growth-factor signaling pathways, specifically abrogate the requirement for mitogens of the EGF pathway. Examples of such genes include the erbB/EGF receptor and erbB-2, which encode structurally related receptor proteins and are often amplified and/or overexpressed in epithelial malignancies. Employing reduced stringency hybridization with v-erbB as a probe, we recently identified a third member of this receptor family, designated erbB-3. cDNA cloning revealed a predicted 148-kD transmembrane polypeptide with structural features similar to those of the EGF receptor. Normal erbB-3 expression in keratinocytes and glandular epithelium suggests its physiologic role in these cell types. Moreover, markedly elevated erbB-3 mRNA levels in certain mammary tumor cell lines suggest that increased erbB-3 expression may also play a role in some human epithelial malignancies.
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PMID:Growth factor-regulated pathways in epithelial cell proliferation. 225 77

The protein product of the rodent neu oncogene, p185neu, is a tyrosine kinase with structural similarity to the epidermal growth factor receptor (EGFR). Transfection and subsequent overexpression of the human p185c-erbB-2 protein transforms NIH 3T3 cells in vitro. However, NIH 3T3 cells are not transformed by overexpressed rodent p185c-neu. NIH 3T3 transfectants overexpressing EGF receptors are not transformed unless incompletely transformed. Several groups have recently demonstrated EGF-induced, EGFR-mediated phosphorylation of p185c-neu. During efforts to characterize the interaction of p185c-neu with EGFR further, we created cell lines that simultaneously overexpress both p185c-neu and EGFR and observed that these cells become transformed. These observations demonstrate that two distinct, overexpressed tyrosine kinases can act synergistically to transform NIH 3T3 cells, thus identifying a novel mechanism that can lead to transformation.
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PMID:Synergistic interaction of p185c-neu and the EGF receptor leads to transformation of rodent fibroblasts. 256 88

DNAs from 37 human gastric carcinomas and seven lymph node metastases were analyzed for alterations of the epidermal growth factor receptor (EGFR) gene and oncogenes by the Southern blot hybridization method. The probes used were EGFR gene, c-Ha-ras, v-Ki-ras, N-ras, c-myc, v-myb, v-fos, c-erbB-2, v-erbA, v-abl and v-fes. Amplification of the EGFR gene was detected in only one poorly differentiated adenocarcinoma. Amplifications of c-myc gene and c-erbB-2 gene were each observed in two well differentiated adenocarcinomas. One of these tumors had coamplification of c-erbB-2 and c-erbA genes but there were no amplifications nor rearrangements of other oncogenes. The poorly differentiated adenocarcinom with amplified EGFR gene also showed enhanced expression of EGFR gene by Northern blot analysis and additionally had strong synchronous immunoreactivity for EGFR and EGF.
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PMID:Amplification of epidermal growth factor receptor (EGFR) gene and oncogenes in human gastric carcinomas. 257 Apr 89

The epidermal growth factor receptor (EGF-R) and the erbB-2 proto-oncogene product protein are closely related by their structural homology and their shared enzymatic activity as autophosphorylating tyrosine kinases. We show that in mammary tumor cells (SK-BR-3) EGF causes a rapid increase in tyrosine phosphorylation of the erbB-2 protein. Phosphorylation of erbB-2 does not occur in cells lacking the EGF-R (MDA-MB-453). Phosphorylation of erbB-2 in SK-BR-3 cells is blocked if EGF is prevented from interacting with its receptor by specific monoclonal antibodies. While EGF induces the down-regulation of its receptor in SK-BR-3 cells, EGF has no effect on the stability of the erbB-2 protein. This result suggests that the erbB-2 protein is a substrate of the EGF-R and indicates the possibility of communication between these two proteins early in the signal transduction process.
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PMID:Egf binding to its receptor triggers a rapid tyrosine phosphorylation of the erbB-2 protein in the mammary tumor cell line SK-BR-3. 290 52

Amplification and overexpression of proto-oncogenes are associated with the malignant nature of some human tumours. In this study we have determined the prevalence of amplification of the proto-oncogenes c-erb B1 (= epidermal growth factor receptor gene), c-erb B2 and c-myc in 44 human intracranial tumours (27 gliomas, six metastases to the brain and 11 meningiomas). None of the tumours had an amplified c-erb B2 gene and only two tumours had an amplified c-myc gene. Nineteen per cent (five out of 27) of the gliomas, 50% (three out of six) of the brain metastases and 0% (0 out of 11) meningiomas had an amplified EGF-receptor gene. Amplification of the EGF-receptor gene appeared to give a growth advantage when single-cell suspensions of the tumours were grown in agarose.
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PMID:Amplification of the epidermal growth factor receptor gene in biopsy specimens from human intracranial tumours. 290 90

An avian erythroblastosis virus, AEV-H, induces both erythroblastosis and sarcomas in susceptible chickens. Since AEV-H carries the v-erbB as a sole oncogene, the erbB gene was suggested to be responsible for the induction of these tumors. Analysis of the amino acid sequence predicted from the nucleotide sequence of the v-erbB gene revealed that the gene product has a domain characteristic for tyrosine kinase. Recently in has been suggested has the v-erbB protein is a part of the chicken EGF (epidermal growth factor) receptor. Using antibody against either v-erbB protein or EGF receptor, we also demonstrated close similarity between the two proteins. Further studies on human genomic DNA revealed that the c-erbB-1 gene, a proto-oncogene of the v-erbB gene, is the EGF receptor gene. We were also able to identify the c-erbB-2 gene that seems to code for a EGF receptor-like protein with a domain for tyrosine kinase. Finally, we would like to show that cell lines established from human squamous cell carcinom are frequently associated with amplification of the c-erbB-1/EGF receptor gene.
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PMID:[A member of the SRC gene family, the c-erbB-1 gene, is closely related to the EGF receptor gene]. 298 99

Two synthetic peptides from the predicted sequence of the human c-erbB-2 protein were synthesized and used to raise antisera in rabbits. The sequences chosen were identical to those in the homologous rat c-neu protein. The antibodies produced reacted with the immunizing peptides in ELISA but showed little or no cross-reaction with the partly homologous peptides found in equivalent positions in the human EGF receptor. Both antipeptide antibodies, and a monoclonal antibody (MAb) specific for the rat neu protein, immunoprecipitated a 185-kDa protein from 35S-methionine-labelled lysates prepared from a rat cell line known to express high levels of the c-neu protein. The antipeptide antibodies also recognized a protein of the same size in Western blots. In addition, both antipeptide antibodies immunoprecipitated a 190-kDa protein from labelled cell lysates prepared from human and monkey cells. Antibodies to one of the peptides, which showed no detectable cross-reaction with human, rat or monkey EGF receptor, were used to examine the expression of the c-erbB-2 protein on a variety of cultured cell types. Eleven transformed, I non-established and 2 immortalized cell types were examined by immunoprecipitation for their level of expression of the c-erbB-2 protein and of the EGF receptor. The numbers of EGF receptors varied widely between different cell lines, whereas the level of the c-erbB-2 protein, which was found on all of the cell types examined, was more constant. The number of c-erbB-2 molecules present was estimated by autoradiography to be about 100,000 per cell. The antibodies were then used to examine the location and level of expression of the human c-erbB-2 and rat c-neu proteins in normal tissues. Immunohistochemical staining showed that the c-erbB-2 protein was highly expressed in rat kidney proximal tubules and loop of Henle. The c-erbB-2 protein was also present on normal human epithelial cells but in some cases with a different distribution to that of the EGF receptor.
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PMID:Expression of the c-erbB-2 protein in normal and transformed cells. 330 94

We have determined the total coding sequence of human c-yes, a non-receptor type protein-tyrosine kinase gene, and found that the c-yes gene closely resembles the c-src gene. Recently, two new genes, syn and lyn, were found to encode proteins closely related to the yes product. In addition, we also determined the partial sequence of fgr. These genes together with lck reported by two American groups have very closely related structures and are thought to compose a closely related group of non-receptor type protein-tyrosine kinases. Partial analysis of the structures of these genes indicated that they have identical splicing junctions at all sites so far examined. On the other hand, the erbB-1/EGF (epidermal growth factor) receptor gene and the erbB-2/neu gene have completely different splicing junctions from those of the above gene group even in the kinase domain, although these genes also have protein kinase activity specific for tyrosine residues and the erbB-1 and -2 genes share splicing sites. These results suggest that the genes of the group of six non-receptor type kinases and those of the erbB-1 and erbB-2 gene group are descendants evolved by duplication of two distinct ancestor genes and are members of two distinct multi-gene families. The genes coding for protein kinases may be members of a super-family including multiple distinct gene families.
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PMID:Nakahara memorial lecture. Non-receptor type protein-tyrosine kinases closely related to src and yes compose a multigene family. 333 5

The c-erbB-2 gene was first identified by virtue of its cross-hybridization with v-erbB. Nucleotide sequence analysis of complementary DNA clones suggested that the c-erbB-2 gene encodes a growth factor receptor similar to that for EGF. Antibodies against the carboxyl terminal sequence of the c-erbB-2 protein immunoprecipitated a 185-kDa glycoprotein which showed protein-tyrosine kinase activity in vitro. Despite the extensive similarity between the c-erbB-2 protein and EGF receptor, neither EGF nor TGF-alpha bound to the c-erbB-2 protein. Phosphorylation of the c-erbB-2 protein was stimulated by TPA via protein kinase C in vivo. EGF also induced phosphorylation of the c-erbB-2 protein. This phosphorylation occurred not only on serine and threonine residues but also on tyrosine residues. Preliminary data suggested that the latter was mediated by the kinase activity of the EGF receptor. Southern blot analysis of DNAs from primary tumors revealed that the c-erbB-2 gene tends to be amplified in adenocarcinomas, mostly of the stomach and the breast. By screening both human genomic and cDNA libraries using v-yes DNA as a probe, we obtained DNA clones of the c-yes gene, the pseudogene of c-yes, c-fgr gene and c-src gene and two novel yes-related genes, fyn and lyn. Complete nucleotide sequence analysis of the cDNA clones of c-yes, fyn and lyn revealed that these genes encode proteins similar to p60src both in size and sequence.
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PMID:[The erbB-related protooncogenes encoding growth factor receptors]. 349 52


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