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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. (2007) Characterization of the cell membrane-associated products of the Neuregulin 4 gene. Oncogene, 27 (5). pp. 715-720. ISSN 1476-5594. (doi:10.1038/sj.onc.1210689) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1038/sj.onc.1210689

Abstract

The NRG4 gene is a member of a family of four genes that 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 stabilization 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 biological 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 green fluorescent protein-tagged proteins and immunofluorescent staining with specific anti-peptide antibodies showed that NRG4A1 is localized 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
R Medicine
R Medicine > RS Pharmacy and materia medica
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Stewart Brownrigg
Date Deposited: 07 Mar 2014 00:05 UTC
Last Modified: 29 May 2019 12:24 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/40423 (The current URI for this page, for reference purposes)
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