Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retroviral vectors pDOL/NeuN and pDOL/NeuT were used to express normal and transforming rat neu cDNAs in PC12 cells. DOL/NeuT-infected cells exhibited a high frequency of spontaneous neurite outgrowth while DOL/NeuN-infected cells showed neurite outgrowth in the presence of heregulin, a putative ligand for the neu receptor tyrosine kinase. In both cases, neurite outgrowth was preceded by phosphorylation of p185neu and several other cellular proteins. Thus the neu tyrosine kinase can elicit morphological and biochemical changes resembling, but distinct from, those stimulated by NGF, and heregulin stimulates neu to elicit these effects in PC12 cells.
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PMID:Oncogenically activated or ligand-stimulated neu kinase stimulates neurite outgrowth in PC12 cells. 791 94

Receptor tyrosine kinases play essential roles in morphogenesis and differentiation of epithelia. Here we examined various tyrosine kinase receptors, which are preferentially expressed in epithelia (c-met, c-ros, c-neu, and the keratin growth factor [KGF] receptor), for their capacity to induce cell motility and branching morphogenesis of epithelial cells. We exchanged the ligand-binding domain of these receptors by the ectodomain of trkA and could thus control signaling by the new ligand, NGF. We demonstrate here that the tyrosine kinases of c-met, c-ros, c-neu, the KGF receptor, and trkA, but not the insulin receptor, induced scattering and increased motility of kidney epithelial cells in tissue culture. Mutational analysis suggests that SHC binding is essential for scattering and increased cell motility induced by trkA. The induction of motility in epithelial cells is thus an important feature of various receptor tyrosine kinases, which in vivo play a role in embryogenesis and metastasis. In contrast, only the c-met receptor promoted branching morphogenesis of kidney epithelial cells in three-dimensional matrices, which resemble the formation of tubular epithelia in development. Interestingly, the ability of c-met to induce morphogenesis could be transferred to trkA, when in a novel receptor hybrid COOH-terminal sequences of c-met (including Y14 to Y16) were fused to the trkA kinase domain. These data demonstrate that tubulogenesis of epithelia is a restricted activity of tyrosine kinases, as yet only demonstrated for the c-met receptor. We predict the existence of specific substrates that mediate this morphogenesis signal.
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PMID:Motogenic and morphogenic activity of epithelial receptor tyrosine kinases. 865 82

The effects of heregulin on the cell line HB2, derived from immortalised human luminal mammary epithelial cells, have been examined. HB2 cells, which normally form smooth spherical colonies in collagen gels, exhibited a striking heregulin-induced morphological change to colonies projecting a large number of spiky branches. A mitogenic effect of heregulin on HB2 cells was also seen, which was more pronounced on collagen than on plastic, whereas cell motility was unaffected. HB2 cells were found to express the heregulin receptor subunits HER2 and HER3, but not HER4. Treatment of HB2 cells with heregulin also induced tyrosine phosphorylation of a band shown by immunoprecipitation to contain HER3. Using specific receptor-blocking antibodies, it was found that both the morphogenetic and proliferative responses of heregulin in HB2 cells were mediated by HER2 and HER3. To compare the effects of HER2 in heregulin signaling to heregulin-independent HER2 homodimerisation (thought to be a carcinoma-associated event), HB2 cells were transfected with the trk-neu hybrid receptor which could be induced to form homodimers by NGF. Although activated HER2 homodimers induced proliferation in the HB2 transfectants in collagen, a morphological response in collagen was not seen, suggesting that HER3 signaling is important for morphogenesis in this cell type.
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PMID:Morphogenetic and proliferative responses to heregulin of mammary epithelial cells in vitro are dependent on HER2 and HER3 and differ from the responses to HER2 homodimerisation or hepatocyte growth factor. 1081 78