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)

The epidermal growth factor (EGF) receptor activates several signaling cascades in response to the ligands EGF and amphiregulin (AR). One of these signaling events involves the tyrosine phosphorylation of STATs (signal transducers and activators of transcription), a process believed to require the activation of a tyrosine kinase of the JAK family. In this report we demonstrate that EGF- and AR-induced STAT activation requires the intrinsic kinase activity of the receptor but not the presence of Jak1. We show that both wild type (WT) and truncated EGF receptors lacking all autophosphorylation sites activate STAT 1, 3, and 5 in response to either EGF or AR. Furthermore, relative to cells expressing WT receptor, ligand-induced tyrosine phosphorylation of the STATs was enhanced in cells expressing only the truncated receptor. These results provide the first evidence that (i) EGF receptor-mediated STAT activation occurs in a Jak1-independent manner, (ii) the intrinsic tyrosine kinase activity of the receptor is essential for STAT activation, and (iii) tyrosine phosphorylation sites within the EGF receptor are not required for STAT activation.
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PMID:STAT activation by epidermal growth factor (EGF) and amphiregulin. Requirement for the EGF receptor kinase but not for tyrosine phosphorylation sites or JAK1. 862 73

Overexpression of the growth factor receptor ErbB-2/Her2/Neu has been implicated in the development of non-small-cell lung cancer. We have reported that the transformation of human lung epithelial cells by c-erbB-2 also requires an active ErbB-1 (EGF receptor) and the autocrine production of its ligand, TGF-alpha. In this report, we demonstrate that STAT 3 is constitutively activated in these cells by the TGF-alpha-stimulated ErbB-1/-2 heterodimer complex. STAT 3 activation was confirmed by mobility shift assays and nuclear localization. ErbB-1 was required, but not sufficient for the TGF-alpha-induced activation of STATs. Inhibition of ErbB-2 kinase activity by tyrphostin AG825 prevented the constitutive activation of STAT 3 in the TGF-alpha-producing, ErbB-1 expressing cell line. Our results demonstrate a requirement for ErbB-2 kinase activity to establish constitutive STAT 3 activation resulting from an autocrine ErbB-1/ TGF-alpha loop. Int. J. Cancer 83:564-570, 1999. Published 1999 Wiley-Liss, Inc.
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PMID:ErbB-2 kinase is required for constitutive stat 3 activation in malignant human lung epithelial cells. 1050 95

The method described here employs a high-content cell-based assay format for the detection of neutralizing antibodies (NAbs) to panitumumab, a fully human monoclonal antagonistic antibody to the human epidermal growth factor (EGF) receptor in human serum (screening assay). A specificity assay was also developed and qualified to confirm that the neutralizing activity was attributable to the presence of NAbs and not due to serum interference (serum interference assay). The ArrayScan IV HCS reader was used for the measurement of tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) and STAT-1 redistribution between the cytoplasm and nucleus in the human epidermoid carcinoma cell line A431. Assay conditions were developed by (1) optimizing the response of the A431 cells to recombinant human EGF in pooled human serum, (2) evaluating the ability of panitumumab to inhibit the EGF response, and (3) assessing the assay's sensitivity for detecting a positive control affinity purified rabbit polyclonal anti-panitumumab antibody. Panitumumab dose-dependently inhibited 4 ng/mL EGF, and the positive control antibody showed a dose-dependent neutralization of 50 ng/mL panitumumab. The experiments indicated that in comparison to STAT-1 translocation, EGFR phosphorylation was the optimal endpoint for the screening and serum interference assays. Assay cut points were derived for the screening and serum interference assays by obtaining normalized ratios of mean fluorescence intensity values obtained with EGFR phosphorylation by testing sera from healthy human donor sera. The assay sensitivity was determined to be 0.125 microg/mL for the positive control antibody.
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PMID:Multiplexed evaluation of a cell-based assay for the detection of antidrug neutralizing antibodies to panitumumab in human serum using automated fluorescent microscopy. 2050 54

For the firsts time, the involvement of the STAT pathway in the regulation of neuronal apoptosis in physiological aging and in old mice overexpressing the HER-2/neu oncogene was studied. We showed that suppression of STAT3, STAT5, and STAT6 and overexpression of the proapoptotic factor STAT1, which provides p53-mediated apoptosis, are the causes for increasing the number of apoptotic neurons in physiological aging. HER-2 tyrosine kinase receptor overexpression promotes neuronal survival through activation of STAT-signaling pathway with simultaneous suppression of the proapoptotic factor STAT1.
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PMID:The role of STAT transcription factors in apoptosis regulation of hypothalamic neurons in aging in HER-2/neu transgenic mice and wild-type FVB/N mice. 2741 25