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)

A human yeast artificial chromosome (YAC) library was screened by polymerase chain reaction with oligonucleotide primers defined for DNA sequences of the BCR gene and the protooncogenes c-raf-1, c-fms, and c-erbB-2. Alu-PCR-generated human DNA sequences were obtained from the respective YAC clones and used for fluorescence in situ hybridization experiments under suppression conditions. After chromosomal in situ suppression hybridization to GTG-banded human prometaphase chromosomes, seven of nine initially isolated YAC clones yielded strong signals exclusively in the chromosome bands containing the respective genes. Two clones yielded additional signals on other chromosomes and were excluded from further tests. The band-specific YACs were successfully applied to visualize specific structural chromosome aberrations in peripheral blood cells from patients with myelodysplasia exhibiting del(5)(q13q34), chronic myeloid leukemia and acute lymphocytic leukemia with t(9;22)(q34;q11), acute promyelocytic leukemia (M3) with t(15;17)(q22;q21), and in a cell line established from a proband with the constitutional translocation t(3;8)(p14.2;q24). In addition to the analysis of metaphase spreads, we demonstrate the particular usefulness of these YAC clones in combination with whole chromosome painting to analyze specific chromosome aberrations directly in the interphase nucleus.
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PMID:Metaphase and interphase cytogenetics with Alu-PCR-amplified yeast artificial chromosome clones containing the BCR gene and the protooncogenes c-raf-1, c-fms, and c-erbB-2. 156 26

The Shc gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc proteins are ubiquitously expressed and are downstream targets and effectors of activated tyrosine kinases (TK). We investigated tyrosine-phosphorylation of Shc proteins in normal and transformed cells. In tumor cells with known TK gene alterations Shc proteins were constitutively phosphorylated and complexed with the activated TK. No constitutive Shc phosphorylation was found in primary cell cultures and normal tissues. In 14 of 27 tumor cell lines with no reported TK alterations, Shc proteins were constitutively phosphorylated and formed stable complexes with novel tyrosine-phosphorylated polypeptides. Ten distinct Shc-associated phosphoproteins were identified with molecular weights ranging from 30 to 200 kDa. In a subset of carcinoma cell lines, phosphorylated Shc proteins complexed with a p175 phosphoprotein that was identified as the constitutively activated EGFR. In one glioblastoma cell line, a Shc-associated p190 was identified as the activated PDGFR. In 13 of 14 acute leukemia samples phosphorylated Shc proteins were constitutively complexed with a p140 phosphoprotein. Some of the Shc-associated phosphoproteins (EGFR, PDGFR, erbB-2, Met, bcr-abl, H4-ret) bound both the Shc- and Grb2-SH2 domains in vitro; others (p175; p70-p80) only the Shc-SH2 domain and yet others (p140) only the Grb2-SH3 domains. These results indicate that Shc proteins are common substrates of constitutively activated TKs and that the analysis of Shc phosphorylation allow the identification of tumors with constitutive TK activation.
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PMID:Constitutive phosphorylation of Shc proteins in human tumors. 767 49

The protooncogene protein-tyrosine kinase c-fes plays an active role in the induction of terminal myeloid differentiation in myeloid leukemia cells. Although p93c-fes contains two autophosphorylation sites, it is not known what role they play in its catalytic or biological activities. To address this question, the major autophosphorylation site at tyrosine 713 was mutated to phenylalanine (YF713), and the mutated cDNA was expressed in a baculovirus system to assess catalytic activity, as well as in an inducible retrovirus to determine its biological activity. The major phosphopeptide in p93c-fes in vitro contained Y713 and was absent in the YF713 mutant, which exhibited an 85% loss of autophosphorylation activity. The catalytic activity of p93c-fesYF713 with either RCM-lysozyme or poly(Glu,Tyr)4:1 as substrate was reduced by 85 and 78%, respectively, in comparison to p93c-fes. Retroviral infection of K562 cells with the c-fes cDNA under the control of the mouse metallothionein promoter increased superoxide formation, phagocytosis, CD13 and CD33 antigen expression, and doubling time 4-6 days after induction. Cells infected with c-fesYF713 exhibited 40% less superoxide formation but similar levels of phagocytosis, CD13/CD33 antigen, and doubling time in comparison to cells infected with c-fes. The level of phosphotyrosine-containing proteins did not markedly differ between K562 cells expressing either neo, c-fes, or c-fesYF713, with the exception of a reduction in the level of a 210-kDa protein specifically in both c-fes-expressing cell lines. The p210 was tentatively identified as bcr-abl, whose level was also reduced in cells expressing c-fes or c-fesYF713.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the mutation of tyrosine 713 in p93c-fes on its catalytic activity and ability to promote myeloid differentiation in K562 cells. 833 28

Four analogues of AG957, a known inhibitor of the tyrosine kinase p210(bcr-abl), have been synthesized and tested for their growth inhibitory effect against the BCR/ABL-positive FDrv210C cells as well as the epidermal growth factor (EGF) receptor-positive Baf/ERX cells. All compounds that can undergo oxidation to the corresponding quinone demonstrated inhibition of FDrv210C cells and Baf/ERX cells. Compounds that cannot become oxidized showed significantly less inhibition of BCR/ABL- or EGF receptor-mediated cell proliferation. The (11)C-labeled compounds were prepared by labeling 4-aminobenzoic acid using [(11)C]CH(3)I, which afforded the corresponding (11)C-labeled methyl ester in excellent yields. Subsequent condensation of the amino group with an appropriately substituted hydroxy benzaldehyde formed the respective Schiff base. Reduction of this compound with NaBH(3)CN gave the (11)C-labeled inhibitors in an overall radiochemical yield of 17.3+/-2.1% (n=3; not decay corrected) and an average specific radioactivity of 40 GBq/micromol (1.1 Ci/micromol) at the end of synthesis. The total synthesis time from EOB including HPLC purification and formulation was 45 min.
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PMID:Synthesis, 11C labeling and biological properties of derivatives of the tyrphostin AG957. 1587 1