A Neu Differentiation Factor (NDF) Domain Essential for Proliferation and Alterations in Morphology of Colonic Epithelial CellsIn Vitro

Whoriskey, John; Pekar, Susan K.; Elliott, Gary; Hara, Shinichi; Liu, Naili; Lenz, D. M.; Zamborelli, Thomas J.; Mayer, John P.; Tarpley, J. E.; Ratzkin, Barry; Yoshinaga, Steven K.

doi:10.3109/08977199809017485

Cited by 7 publications

(5 citation statements)

References 47 publications

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“…repair of the epithelium itself, especially as the NRG-1␣ isoforms are not up-regulated in the olfactory bulb (Meyer et al,1997;al Moustafa et al, 1999). NRG-1s have been reported to induce morphological changes and proliferation in epithelial cells of different origins (Chausovsky et al, 1998;Whoriskey et al, 1998) In addition, NRG-1␣2 has been found to be present in epidermis during tissue repair (Danilenko et al, 1995;Ram et al, 1995). Changes were also seen in the type 1␤ isoform with regards to the presence or absence of the spacer domain.…”

Section: Mrna Expression Of Nrg-1 Isoforms In the Olfactory System Afmentioning

confidence: 80%

Comparison of neuregulin-1 expression in olfactory ensheathing cells, Schwann cells and astrocytes

et al. 2000

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Section: Mrna Expression Of Nrg-1 Isoforms In the Olfactory System Afmentioning

confidence: 80%

Comparison of neuregulin-1 expression in olfactory ensheathing cells, Schwann cells and astrocytes

et al. 2000

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“…Such a process may be involved in the development of tumorigenesis [31]. In vitro, Nrg1 acts to stimulate the proliferation and alters the cellular morphology of colonic epithelial cells in culture, with Nrg1b exhibiting more pronounced effects than the alpha isoform [32]. NRG4 and ErbB4 were also found to be mainly expressed in mucosa-associated lymphoid tissue (MALT) and follicular lymphoma, where they function in the proliferation of malignant lymphoma cells in the GI tract [33].…”

Section: Discussionmentioning

confidence: 99%

The expression and localization of neuregulin-1 (Nrg1) in the gastrointestinal system of the rhesus monkey

Zhao

2013

Folia Histochem Cytobiol.

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Although Neuregulin-1 (Nrg1) and its cognate receptors have been found at the mRNA level in human gastrointestinal (GI) tract and their functional roles have been evaluated in vitro, their morphological distribution in higher mammals are not fully elucidated. The present research focused on morphological distribution of Nrg1 and its receptors, ErbB2 and ErbB4, in main GI tissues of the non-human primate rhesus monkey. The morphological expression of Nrg1 and its ErbB2 and ErbB4 receptors as well as their potential colocalization were determined by double immunofluorescence staining in esophagus, stomach, small intestine and colon tissues derived from the rhesus monkey tissue microarray. The Nrg1 level on each sample was indexed by the fold of integrated fluorescence intensity (IFI) relative to that of one brain cortical tissue from the rhesus monkey. Differential expression of Nrg1 and its receptors ErbB2 and ErbB4 was found in the GI structures, with higher expression levels detected in stomach and small intestine. Co-localization of Nrg1 with ErbB2 and/or ErbB4 receptors was most apparently detected in the stomach, followed by small intestine, colon, and esophagus. This investigation morphologically profiles the differential expression of Nrg1 and its receptors in main GI structures, suggesting an autocrine or paracrine loop-directed Nrg1/ErbB receptor signaling pathway in these organs of higher mammals.

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“…Exchange studies between NRG-1␣ and NRG-1␤ show that particularly the linear C-terminal region determines the binding properties and mitogenic potential of these isoforms (25). Therefore, it has been proposed that NRGs may have a bivalent character and interact with both ErbB-3 and ErbB-2 through separate binding sites (26).…”

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confidence: 99%

Selective Formation of ErbB-2/ErbB-3 Heterodimers Depends on the ErbB-3 Affinity of Epidermal Growth Factor-like Ligands

Stortelers

Woning

Jacobs-Oomen

et al. 2003

Journal of Biological Chemistry

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EGF-like growth factors activate their ErbB receptorsby promoting receptor-mediated homodimerization or, alternatively, by the formation of heterodimers with the orphan ErbB-2 through an as yet unknown mechanism. To investigate the selectivity in dimer formation by ligands, we have applied the phage display approach to obtain ligands with modified C-terminal residues that discriminate between ErbB-2 and ErbB-3 as dimerization partners. We used the epidermal growth factor/ transforming growth factor ␣ chimera T1E as the template molecule because it binds to ErbB-3 homodimers with low affinity and to ErbB-2/ErbB-3 heterodimers with high affinity. Many phage variants were selected with enhanced binding affinity for ErbB-3 homodimers, indicating that C-terminal residues contribute to the interaction with ErbB-3. These variants were also potent ligands for ErbB-2/ErbB-3 heterodimers despite negative selection for such heterodimers. In contrast, phage variants positively selected for binding to ErbB-2/ErbB-3 heterodimers but negatively selected for binding to ErbB-3 homodimers can be considered as "second best" ErbB-3 binders, which require ErbB-2 heterodimerization for stable complex formation. Our findings imply that epidermal growth factor-like ligands bind ErbB-3 through a multi-domain interaction involving at least both linear endings of the ligand. Apparently the ErbB-3 affinity of a ligand determines whether it can form only ErbB-2/ErbB-3 complexes or also ErbB-3 homodimers. Because no separate binding domain for ErbB-2 could be identified, our data support a model in which ErbB heterodimerization occurs through a receptor-mediated mechanism and not through bivalent ligands.The recent determination of the crystal structure of the extracellular domain of ErbB-1 in complex with its ligands epidermal growth factor (EGF) 1 or transforming growth factor ␣ (TGF-␣) has provided evidence for the formation of homodimeric ErbB-1 complexes through a receptor-mediated dimerization mechanism (1, 2). Ligand binding to both domains I and III of the extracellular domain of the receptor involves the transition of ErbB-1 from a "closed" to an "open" state, which then permits dimerization with another liganded ErbB-1 through interaction of domain II residues within these receptors. Most likely this mechanism can serve as a paradigm for homodimerization of other liganded ErbB receptors, such as ErbB-3 and ErbB-4. However, it is well established that EGFlike growth factors preferentially signal through heterodimers of their cognate receptor with the orphan ErbB-2. The mechanism by which EGF-like growth factors bind their receptors in heterodimeric receptor complexes remains an open question.Dimerization of ligand-bound receptor tyrosine kinases is a mechanism that is thought to activate the intrinsic kinase domain followed by transphosphorylation and subsequent docking of cellular signal transducing proteins. As a consequence, ligand binding serves as a potential site for regulation of cell proliferation in diseases where ErbB rece...

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A Neu Differentiation Factor (NDF) Domain Essential for Proliferation and Alterations in Morphology of Colonic Epithelial CellsIn Vitro

Cited by 7 publications

References 47 publications

Comparison of neuregulin-1 expression in olfactory ensheathing cells, Schwann cells and astrocytes

Comparison of neuregulin-1 expression in olfactory ensheathing cells, Schwann cells and astrocytes

The expression and localization of neuregulin-1 (Nrg1) in the gastrointestinal system of the rhesus monkey

Selective Formation of ErbB-2/ErbB-3 Heterodimers Depends on the ErbB-3 Affinity of Epidermal Growth Factor-like Ligands

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