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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neu gene, which encodes a putative tyrosine kinase growth factor receptor termed p185neu, was originally identified as a dominant transforming gene in neurogliomas and schwannomas induced by transplacental treatment of rat embryos with ethylnitrosourea. The present studies were undertaken to determine the expression pattern of the neu gene in peripheral nerve. Northern blot analysis of total RNA isolated from rat sciatic nerves demonstrated prominent neu mRNA expression on postnatal days 1 and 7, with substantially lower expression up to adulthood. Immunohistochemical studies confirmed expression of p185neu by Schwann cells (SC) in developing sciatic nerve and minimal p185neu immunoreactivity in adult nerves. However, neu mRNA and p185neu protein progressively increased following sciatic nerve transection in adult animals. In addition, neu mRNA and p185neu were found in neonatal rat sciatic nerve SC and several SC-derived cell lines. In resting SC, neu mRNA was expressed at a low level, but was greatly increased by treatment with forskolin and glial growth factor. These studies demonstrate that the neu gene and its protein product, p185neu, are expressed by SC both in vivo and in vitro and suggest that p185neu plays a role in the regulation of SC proliferation or differentiation.
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PMID:Expression of the neu proto-oncogene by Schwann cells during peripheral nerve development and Wallerian degeneration. 137 76

The receptor erbB2/neu is a member of the epidermal growth factor receptor (EGFR or erbB) family that also includes erbB3 and erbB4. Amplification of the erbB2/neu gene is found in many cancer types and its overexpression is correlated with a poor prognosis for breast and ovarian cancer patients. Investigation of the biology of erbB2 led to the identification of a family of ligands termed neuregulins which included the neu-differentiation factors, the heregulins, a ligand with acetylcholine-receptor-inducing activity and glial growth factor. Several lines of evidence suggest that heterodimerization of erbB2 with other erbB receptors is required for neuregulin signalling. Here we investigate the developmental role of erbB2 in mammalian development in mice carrying an erbB2 null allele. We find that mutant embryos die before E11, probably as a result of dysfunctions associated with a lack of cardiac trabeculae. Development of cranial neural-crest-derived sensory ganglia was markedly affected. DiI retrograde tracing revealed that the development of motor nerves was also compromised. Our results demonstrate the importance of erbB2 in neural and cardiac development.
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PMID:Requirement for neuregulin receptor erbB2 in neural and cardiac development. 747 64

The long-term propagation of primary human prostate cancer (PCA) in vivo or in vitro has been rare. Most such PCAs are phenotypically different from most PCAs in humans; i.e., they make little prostate specific antigen and respond little, if at all, to androgen deprivation. A serially transplantable, primary human PCA, designated CWR22, exhibits a clonal cytogenetic aberration, causes high elevations of prostate specific antigen in the peripheral blood of nude mice, and is unusually responsive to androgen deprivation as compared with other xenografts. Studies of mRNA from CWR22 have demonstrated the expression of prostate specific antigen and the epidermal growth factor receptor family including erbB1/epidermal growth factor receptor, erbB2/neu, and erbB3, but not erbB4. A ligand for these receptors, the neu differentiation factor, is also expressed.
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PMID:CWR22: androgen-dependent xenograft model derived from a primary human prostatic carcinoma. 752 52

new differentiation factor (NDF), also known as heregulin, is structurally related to the epidermal growth factor family of growth factors; it stimulates tyrosine phosphorylation of the neu/HER-2 oncogene and causes differentiation of certain human breast cancer cell lines. Alternative splicing of a single gene gives rise to multiple isoforms of NDF/heregulin, as well as the neuronal homologues, designated ARIA (acetylcholine receptor inducing activity) and GGF (glial growth factor); at least 15 structural variants are known. All but two of the NDF/heregulin cDNAs are predicted to encode transmembrane, glycosylated precursors of soluble NDF. In this report we characterized the biosynthetic processing of different NDF isoforms in stably transfected Chinese hamster ovary cells expressing individual NDF isoforms, and in the native cell line Rat 1-EJ, which expresses at least six different NDF isoforms. We found that the precursors for NDF undergo typical glycosylation and trafficking. A portion of the molecules are proteolytically cleaved intracellularly leading to the constitutive secretion of soluble, mature NDF into the culture media. However, a significant portion of the newly synthesized NDF precursor molecules escape intracellular cleavage and are transported to the cell surface of both transfected and native cells, where they reside as full-length, transmembrane proteins. Finally we show that these full-length, transmembrane NDF molecules can undergo phorbol ester regulated cleavage from the membrane, releasing the soluble growth factor into the medium.
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PMID:Biosynthetic processing of neu differentiation factor. Glycosylation trafficking, and regulated cleavage from the cell surface. 764 87

The HER4/erbB-4 gene has been isolated as the fourth member of the human EGFR subfamily of tyrosine kinases and has been reported to encode a receptor for NDF/heregulin. In the present study we determined the chromosomal location of the HER4/erbB-4 gene within the human genome. Using human cDNA probes in fluorescence in situ hybridization (FISH), we mapped the HER4/erbB-4 gene to human chromosome 2q33.3-34. This finding established that also the HER4/erbB-4 gene is located in close vicinity of homeobox and collagen gene loci, as is the case for the related EGFR, erbB-2/neu and erbB-3. Aberrations of this chromosomal region associated with T cell leukemias and lymphomas as well as alveolar rhabdomyosarcomas raise the possibility that HER4/erbB-4 might be activated in these tumour types.
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PMID:Localization of the human HER4/erbB-4 gene to chromosome 2. 770 Jun 49

Transmembrane receptor tyrosine kinases that bind to peptide factors transmit essential growth and differentiation signals. A growing list of orphan receptors, of which some are oncogenic, holds the promise that many unknown ligands may be discovered by tracking the corresponding surface molecules. The neu gene (also called erbB-2 and HER-2) encodes such a receptor tyrosine kinase whose oncogenic potential is released in the developing rodent nervous system through a point mutation. Amplification and overexpression of neu are thought to contribute to malignancy of certain human adenocarcinomas. The search for soluble factors that interact with the Neu receptor led to the discovery of a 44 kDa glycoprotein that induces phenotypic differentiation of cultured mammary tumor cells to growth-arrested and milk-producing cells. The Neu differentiation factor (NDF or heregulin), however, also acts as a mitogen for epithelial, Schwann and glial cells. Multiple forms of the factor are produced by alternative splicing and their expression is confined predominantly to the central and to the peripheral nervous systems. One identified neuronal function of this family of polypeptides is to control the formation of neuromuscular junctions, but their physiological role in secretory epithelia is still unknown. Other open questions relate to the transmembrane topology of various precursors, the identity of a putative coreceptor, the possible existence of additional ligands of Neu and the functional significance of the interaction between Neu and at least three highly related receptor tyrosine kinases.
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PMID:Neu and its ligands: from an oncogene to neural factors. 790 91

Motor neurons stimulate their postsynaptic muscle targets to synthesize neurotransmitter receptors. Polypeptide signaling molecules may mediate this inductive interaction. Here we report the purification of ARIA, a protein that stimulates the synthesis of muscle acetylcholine receptors, and the isolation of ARIA cDNA. Recombinant ARIA increases acetylcholine receptor synthesis greater than 3-fold, and it induces tyrosine phosphorylation of a 185 kd muscle protein. The ARIA cDNA hybridizes with mRNAs that are expressed in the spinal cord from E4, a time prior to the onset of neuromuscular synapse formation, through adulthood. By E7, hybridizing mRNAs are concentrated in motor neurons. Chicken ARIA is homologous to the rat Neu differentiation factor and human here-gulin, ligands for the receptor tyrosine kinase encoded by the neu (c-erbB2, HER2) proto-oncogene. Our data suggest that members of the ARIA protein family promote the formation and maintenance of chemical synapses and, furthermore, that receptor tyrosine kinases play important roles in this process.
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PMID:ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family. 845 70

Using the rat sciatic nerve as a model for the study of Schwann cell differentiation we have identified a Schwann cell precursor, a distinct cell type present in developing nerves at a time when they are projecting to their target tissues. These cells develop into Schwann cells over a relatively short time in vivo. In vitro, they can generate Schwann cells if they are cultured in neuron-conditioned medium or in the presence of neu-differentiation factors (NDF) (neuregulins, heregulins, glial growth factor), a recently discovered family of growth factors expressed at high levels in neurons. Thus neu-differentiation factors may be important neuro-glia signalling molecules in the Schwann cell lineage. Later stages in the development of Schann cells, such as differentiation towards a myelin phenotype, can be studied using cultured Schwann cells. These cells dedifferentiate both in vivo and in vitro when they are deprived of axonal contact. Elevation of intracellular cyclic AMP levels in the absence of cell division causes high levels of expression of Po, the major myelin glycoprotein. TGF beta s and FGFs suppress this induction, while IGFs promote it.
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PMID:Development and differentiation of Schwann cells. 888 21

Recently we identified three novel Schwann cell mitogens named GGF (glial growth factor)-I (34 kDa), GGF-II (59 kDa), and GGF-III (45 kDa), and provided evidence that they are three distinct but structurally related members of a larger family of factors, which includes heregulin, neu differentiation factor, and acetylcholine receptor-inducing activity (ARIA). We report here the characterization of the mitogenic and trophic activities for all three forms of GGF on rat Schwann cells and several other cell types. GGF-I, GGF-II, and GGF-III are potent mitogens for rat Schwann cells in vitro at nanomolar concentrations, whereas at lower concentrations they promote Schwann cell survival, in the absence of cAMP elevating agents. Forskolin, an adenylate cyclase activator, potently synergizes with the GGFs by an indirect mechanism, possibly involving transcriptional activation of GGF receptor(s). In addition, the GGFs stimulate DNA synthesis in rat glioma C6 cells, and in SK-BR-3 cells, which overexpress the p185 neu/erbB2. Fibroblasts obtained from different sources are weakly stimulated by GGFs, whereas PC12 cells are unable to respond under a variety of experimental conditions. These observations are consistent with the proposal that GGF-I, GGF-II, and GGF-III are a set of potent glial cell mitogens and putative ligands of members of the EGF receptor family, namely p185 neu/erbB2, p160/erbB3, and p180/erbB4, which may play important roles in the development, regeneration, and tumor biology of the peripheral nervous system.
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PMID:Glial growth factors I-III are specific mitogens for glial cells. 898 98

The concept is proposed that the central control of mammalian female puberty requires the interactive participation of neuronal networks and glial cells of the astrocytic lineage. According to this concept neurons and astrocytes control the pubertal process by regulating the secretory activity of those neurons that secrete luteinizing hormone-releasing hormone (LHRH). LHRH, in turn, governs sexual development by stimulating the secretion of pituitary gonadotropins. Astrocytes affect LHRH neuronal function via a cell-cell signaling mechanism involving several growth factors and their corresponding receptors. Our laboratory has identified two members of the epidermal growth factor/transforming growth factor (EGF/TGF alpha) family as components of the glial-neuronal interactive process that regulates LHRH secretion. Transforming growth factor alpha (TGF alpha) and its distant congener neu-differentiation factor, NDF, are produced in hypothalamic astrocytes and stimulate LHRH release via a glial intermediacy. The actions of TGF alpha and NDF on hypothalamic astrocytes involve the interactive activation of their cognate receptors and the synergistic effect of both ligands in stimulating the glial release of prostaglandin E2 (PGE2). In turn, PGE2 acts directly on LHRH neurons to stimulate LHRH release. A variety of experimental approaches has led to the conclusion that both TGF alpha and NDF are physiological components of the central mechanism controlling the initiation of female puberty.
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PMID:The transforming growth factor alpha gene family is involved in the neuroendocrine control of mammalian puberty. 932 23


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