Activation of erbB-1 receptors by glial TGFalpha has been shown to be a component of the developmental program by which the neuroendocrine brain controls mammalian sexual development. The participation of other members of the erbB family may be required, however, for full signaling capacity. Here, we show that activation of astrocytic erbB-2/erbB-4 receptors plays a significant role in the proc...

We report a novel approach for specific in vivo inactivation of the ErbB-2 receptor tyrosine kinase and suppression of ErbB-2-induced transformation. Genes encoding single chain antibodies that specifically bind to the extracellular domain of human ErbB-2 were constructed and expressed intracellularly in NIH/3T3 fibroblasts transformed by activated ErbB-2. The single chain antibodies are derive...

BACKGROUND & AIMS Glucagon-like peptide-2 (GLP-2) is a 33-amino acid peptide hormone secreted by enteroendocrine cells in response to nutrient ingestion. GLP-2 stimulates crypt cell proliferation leading to expansion of the mucosal epithelium; however, the mechanisms transducing the trophic effects of GLP-2 are incompletely understood. METHODS We examined the gene expression profiles and grow...

PURPOSE To test the hypothesis that simultaneous, equipotent inhibition of epidermal growth factor receptor (EGFR; erbB1), erbB2 (human epidermal growth factor receptor 2), and erbB3 receptor signaling, using the novel small-molecule inhibitor AZD8931, will deliver broad antitumor activity in vitro and in vivo. EXPERIMENTAL DESIGN A range of assays was used to model erbB family receptor signa...

The ansamycin antibiotic geldanamycin (GA) induces the intracellular degradation of ErbB-2/neu. Degradation of ErbB-2 proceeds through cleavage(s) within the kinase domain, resulting in the formation of a 135 kDa ectodomain fragment and a fragment(s) of approximately 50 kDa containing the COOH-terminal region. On the basis of independent means of identification, two adjacent sequence motifs hav...

c-erbB-2 gene analysis by Southern and DNA dot blot methods was done in 66 tumor samples from patients with histolÃ3gica!!} node-negative breast cancer. The c-erbB-2 gene was amplified 2to >8-fold in 13 tumors (20%). None of 59 tumors that were examined by the Southern method showed c-erbB-2 gene rearrangement. r-erbB-2 amplification was analyzed in relation to other prognostic factors. The c-e...

mAbs capable of disabling heterodimeric kinase complexes of the epidermal growth factor receptor (EGFR) and human EGFR type 2/neu have therapeutic relevance to various human cancers. In this study, we demonstrate that in addition to the dimer, EGFR and human EGFR type 2 can associate as homo- and heterotetramers. EGF-induced phosphorylation of the tetramers was significantly lower than that of ...

Two receptor tyrosine kinases, ErB-3 and ErbB-4, mediate signaling by Neu di€erentiation factors (NDFs, also called neuregulins), while ErbB-1 and ErbB-2 serve as co-receptors. We show that the two NDF/neuregulin receptors di€er in spatial and temporal expression patterns: The kinase-defective receptor, ErbB-3, is expressed primarily in epithelial layers of various organs, in the peripheral ner...

1.1 erbB family HER-2 is a member of the erbB family of receptor tyrosine kinases. Epidermal Growth Factor Receptor (EGFR) was first identified as the cellular homolog of the transduced oncogene of the avian retroviruses such as avian ERythroBlastosis virus, which causes erythroleukemia and fibrosarcoma and gives rise to the family name (erbB). EGFR, as its name implies, was shown by Stanley Co...