Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To provide information about oncogenes for molecular biological studies of tumors in domestic animals, the proto-oncogenes homologous to the c-myc, c-erbB-2, c-ros-1, c-yes-1, v-myc, v-Ki-ras, and v-Ha-ras oncogenes of genomic DNA in cattle, horses, pigs, dogs, cats, and chickens were investigated by Southern blot hybridization. High molecular weight genomic DNA in each of the animals contained proto-oncogenes that had a certain homology with the oncogenes used, but the extent of nucleotide homology of the proto-oncogenes differed in number and molecular weight: ie, 1 or 2 bands at 1.6 to 22.0 kilobase (kb) in the c-myc probe, 1 or 2 bands at 1.1 to 16.0 kb in the c-ros-1 probe, 1 to 3 bands at 0.7 to 23.0 kb in the c-erbB-2 probe, 1 to 4 bands at 0.6 to 18.0 kb in the c-yes-1 probe, 1 to 3 bands at 1.6 to 30.0 kb in the v-myc probe, 1 to 7 bands at 1.0 to 36.0 kb in the v-Ki-ras probe, and 1 to 4 bands at 1.0 to 27.0 kb in the v-Ha-ras probe. Furthermore, signal strength of each band, as determined by autoradiography, was not always the same for each probe in the various animals. Our findings indicate that these proto-oncogenes are well conserved with species specificities in each animal.
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PMID:Proto-oncogenes of genomic DNA in clinically normal animals of various species. 188

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

Overexpression and amplification of the erbB-2 (neu) is thought to play a major role in mammary cancer. Although studies suggest that Neu is directly involved in the genesis of mammary tumors, the molecular mechanism by which Neu induces tumors is not well understood. Recently, we have demonstrated that the activity of c-Src tyrosine kinase is elevated in Neu-induced mammary tumors and this elevated activity correlates with its capacity to physically associate with Neu. To explore whether other members of the c-Src family are activated in these mammary tumors, we measured the in vitro kinase activity of the c-Yes and Fyn kinases in protein extracts derived from mammary tumor tissue and morphological normal adjacent tissue. These analyses revealed that c-Yes kinase activity was elevated in Neu-induced tumors by comparison to the adjacent tissue. By contrast, no significant activation of the Fyn kinase was noted in these tumors. Activation of c-Yes tyrosine kinase correlated with the capacity of c-Yes to associate with Neu in vivo in lysates derived from primary tumor samples. Studies with Rat.2 fibroblasts overexpressing activated Neu revealed that c-Src requires the presence of tyrosine phosphorylated Neu for its ability to interact with Neu in vivo. Moreover, analyses using radiolabeled c-Yes SH2 fusion protein revealed that this interaction is likely occurring in a direct fashion. Although both c-Src and c-Yes kinase associate with Neu in vivo, a tyrosine phosphorylated protein of 89 kd (p89) was found associated with c-Src but not with c-Yes in cell lysates derived from mammary epithelial cells transformed by either Neu or PyV middle T antigen. Furthermore, this tyrosine phosphorylated protein was not detected in c-Src complexes derived from fibroblasts transformed by either Neu or PyV middle T. These observations suggest that p89 associates with c-Src only in mammary epithelial cells and not in fibroblasts.
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PMID:Activation of Src family kinases in Neu-induced mammary tumors correlates with their association with distinct sets of tyrosine phosphorylated proteins in vivo. 747 8

The Src family protein-tyrosine kinases are required for mitogenic signaling from the platelet-derived growth factor (PDGF), colony stimulating factor-1, and epidermal growth factor (EGF) receptor protein-tyrosine kinases (RPTK) (Twamley-Stein, G. M., Pepperkok, R., Ansorge, W., and Courtneidge, S. A. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 7696-7700; Roche, S., Koegl, M., Barone, M. V., Roussel, M. F., and Courtneidge, S. A.(1995) Mol. Cell. Biol. 15, 1102-1109). In NIH3T3 fibroblasts, c-Src, Fyn, and c-Yes associate with the activated PDGF receptor, are substrates for receptor phosphorylation, and are themselves activated. Src family catalytic function is required for RPTK mitogenic signaling as evidenced by the SH2-dependent dominant negative phenotype exhibited by kinase-inactive Src and Fyn mutants (Twamley-Stein, G. M., Pepperkok, R., Ansorge, W., and Courtneidge, S. A.(1993) Proc. Natl. Acad. Sci. U. S. A. 90, 7696-7700). Here, we have generated clonal Src- murine fibroblast cell lines overexpressing various murine c-Src mutants and studied the effect of these mutant Src proteins on PDGF- and EGF-induced mitogenesis. Two c-Src SH3 domain mutants, Y133F and Y138F, each inhibited PDGF BB- and EGF-induced DNA synthesis in quiescent cells. This demonstrates an involvement of the Src SH3 domain in PDGFbeta and EGF receptor mitogenic signaling. Since both Tyr-133 and Tyr-138 are located on the ligand binding surface of the SH3 domain, these results suggest that the c-Src SH3 domain is required for PDGF and EGF mitogenic signaling. The dominant negative effect of either single mutant on PDGF receptor signaling was reversed by a second SH2-inactivating mutation. We conclude that the c-Src SH3 domain function requires the SH2 domain in the case of the PDGF receptor, presumably because binding of c-Src to the receptor via its SH2 domain is a prerequisite for the SH3 domain function. In contrast, SH2 function is apparently not essential for the SH3 function in EGF receptor signaling.
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PMID:Requirement for c-Src catalytic activity and the SH3 domain in platelet-derived growth factor BB and epidermal growth factor mitogenic signaling. 866 29

In order to evaluate the involvement of c-yes and c-erbB-2 oncogene products, and p53 tumor suppressor protein in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 79 mammary tumors were analyzed immunohistochemically using antibodies against human c-yes p62 and c-erbB-2 products and p53. These 79 tumors were divided into 2 groups: 32 benign (2 adenosis, 7 simple adenomas, 14 complex adenomas, and 9 benign mixed mammary tumors) and 47 malignant tumors (26 simple adenocarcinomas, 7 complex adenocarcinomas, 5 solid carcinomas, 2 sclerosing carcinomas, 6 malignant mixed mammary tumors, and 1 malignant myoepithelioma). As a result of immunostaining, 40.6% (13/32) of the benign tumors and 21.3% (10/47) of the malignant tumors expressed the c-Yes oncogene product, ErbB-2 expression was detected in 50% (16/32) of the benign tumors and in 19.1% (9/47) of the malignant tumors. P53 expression was detected in 16% (4/25) of the benign tumors and in 30.6% (11/36) of the malignant tumors. Co-expression of c-Yes and ErbB-2, ErbB-2 and p53, and all 3 products was detected in 6, 1 and 7 tumors, respectively.
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PMID:Immunohistochemical analysis of c-yes and c-erbB-2 oncogene products and p53 tumor suppressor protein in canine mammary tumors. 1002 59

The tyrosine kinase (TK) family includes many growth factor receptors, cell cycle regulators, and oncoproteins. Moreover, the receptor TKs HER2/neu and epidermal growth factor receptor are overexpressed in a subgroup of breast tumors and correlate with more aggressive behavior. Thus, TKs are being actively pursued as therapeutic targets. The purpose of this study was to determine the expression pattern of TKs in breast cancer. Reverse transcription-PCR was performed with degenerate primers based on conserved motifs of the catalytic domains of TKs, and the identities of the reverse transcription-PCR products were determined by digestion with a panel of restriction enzymes. Using a TK display assay, we studied the TK profiles of 13 breast cancer cell lines and two normal immortalized breast epithelial cell lines. The TK display assay reproducibly demonstrated known differences in HER-2/neu expression between cell lines. Several TKs, including receptor TKs Axl, Cak, fibroblast growth factor receptor 4, HEK8, HER2/neu, c-MET, RET, and nonreceptor TKs ARG, BRK, Janus kinase 1, Rak, and YES were detected in breast cancer cells. Several kinases were differentially expressed among the cell lines. Similar TK profiles were found using RNA from human breast tumors. We conclude that there is significant variability in the TK expression pattern of breast cancers. This variability should be considered when selecting TK inhibitors to treat patients.
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PMID:Expression profile of tyrosine kinases in breast cancer. 1183 50

This report describes the profiling of proteins in a sample prepared by laser capture microdissection (LCM) from a breast cancer cell line (SKBR-3). This experimental approach serves as a model system for proteomic studies on selected tissue samples and for studies of specific cell types. The captured cells were isolated in a dehydrated and reduced state and solubilized with a denaturing buffer. After dilution the protein mixture was digested with trypsin and the resulting peptide mixture was fractionated by reversed phase HPLC (RPLC) and analyzed on an ion trap mass spectrometer. A key part of this study is the combination of the LCM process with an extraction/digestion procedure that allowed effective solubilization of a significant part of the cellular sample in a single step. The identity of the peptides was determined by tandem mass spectrometry measurements in which the resulting spectra were compared with genomic and proteomic databases and protein identifications were made. While only peptides with a high probability assignment were used, the interpretation of mass spectral fragmentation patterns were also confirmed by manual interpretation of the spectra. Also, for the more abundant proteins the initial protein assignment from the best match peptide was strengthened by the observation of additional confirmatory peptide identifications. Another selection criteria was correlation of the mass spectrometric studies with clinical and genomic studies of potential cancer markers in tumor samples. This proteomic study allowed identification of the following proteins: human receptor protein kinase HER-2 or ERBB-2 and related kinases HER-3 and HER-4, the gene products from breast cancer type I and II susceptibility genes and cytoskeletal components such as cytokeratins 8, 18 and 19. Other proteins include fibroblast growth factor receptor variants (FGFR-2&4) and T-lymphoma invasion and metastasis inducing protein 1 (TIAM1). In addition several nonreceptor protein kinases YES, FAK and JAK-1 and 3 were identified. Since the study was performed on a limited number of cells (approximately 10,000) it raises the possibility of such studies being performed on individual patient samples prepared by needle biopsy.
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PMID:An approach to the proteomic analysis of a breast cancer cell line (SKBR-3). 1283 28