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Characterization of the cell membrane-associated products of the Neuregulin 4 gene

Hayes, Nandini V. L., Newsam, Ray J., Baines, Anthony J., Gullick, William J. (2008) Characterization of the cell membrane-associated products of the Neuregulin 4 gene. Oncogene, 27 (5). pp. 715-720. ISSN 0950-9232. (doi:10.1038/sj.onc.1210689) (KAR id:7281)


The NRG4 gene is a member of a family of four genes which encode a class of epidermal growth factors. This gene has been reported to express a protein designated here as NRG4A1. We describe here a novel splice variant of the NRG4 gene, NRG4A2 which encodes a C-terminal region containing a predicted type I PDZ binding peptide. Both NRG4A1 and NRG4A2 were shown to be expressed on the cell surface, as expected by the presence of a predicted transmembrane sequence, and were modified at a single N-linked glycosylation site in the extracellular domain. Significant stabilisation of expression of both proteins was seen in the presence of the proteosome inhibitor MG-132 suggesting that they are normally degraded by this system. N-terminal cleavage was inhibited in both isotypes by the broad-spectrum matrix metalloproteinase inhibitor, galardin (GM 6001). A glycosylated, secreted form of NRG4A1 was detected in the cell medium which showed biologically activity in two assays, phosphorylation of the HER4 receptor and stimulation of neurite formation in PC-12 cells stably expressing HER4. Transfection and expression of GFP-tagged proteins and immunofluorescent staining with specific anti-peptide antibodies showed that NRG4A1 is localised to membrane ruffles while NRG4A2 has a more punctate membrane distribution.

Item Type: Article
DOI/Identification number: 10.1038/sj.onc.1210689
Uncontrolled keywords: neuregulin 4; growth factor; tyrosine kinase
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RC Internal medicine > RC254 Neoplasms. Tumors. Oncology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: William Gullick
Date Deposited: 13 Feb 2009 10:25 UTC
Last Modified: 18 Dec 2023 10:22 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Hayes, Nandini V. L..

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Newsam, Ray J..

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Baines, Anthony J..

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Gullick, William J..

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