RGD Reference Report - Neuregulin isoforms exhibit distinct patterns of ErbB family receptor activation. - Rat Genome Database

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Neuregulin isoforms exhibit distinct patterns of ErbB family receptor activation.

Authors: Hobbs, Stuart S  Coffing, Stephanie L  Le, Ann T D  Cameron, Elizabeth M  Williams, Eric E  Andrew, Michelle  Blommel, Erika N  Hammer, Robert P  Chang, Han  Riese, David J 
Citation: Hobbs SS, etal., Oncogene. 2002 Dec 5;21(55):8442-52. doi: 10.1038/sj.onc.1205960.
RGD ID: 151356654
Pubmed: PMID:12466964   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.onc.1205960   (Journal Full-text)

During the last decade, several novel members of the Epidermal Growth Factor family of peptide growth factors have been identified. Most prominent among these are the Neuregulins or Heregulins. To date, four different Neuregulin genes have been identified (Neuregulin1-4) and several different splicing isoforms have been identified for at least two of these genes (Neuregulin1 and Neuregulin2). While Neuregulin1 isoforms have been extensively studied, comparatively little is known about Neuregulin3, Neuregulin4, or the Neuregulin2 isoforms. Indeed, there has been no systematic comparison of the activities of these molecules. Here we demonstrate that Neuregulin2alpha and Neuregulin2beta stimulate ErbB3 tyrosine phosphorylation and coupling to biological responses. In contrast, Neuregulin3 and Neuregulin4 fail to activate ErbB3 signaling. Furthermore, Neuregulin2beta, but not Neuregulin2alpha, stimulates ErbB4 tyrosine phosphorylation and coupling to biological responses. Finally, both Neuregulin3 and Neuregulin4 stimulate modest amounts of ErbB4 tyrosine phosphorylation. However, whereas Neuregulin3 stimulates a modest amount of ErbB4 coupling to biological responses, Neuregulin4 fails to stimulate ErbB4 coupling to biological responses. This suggests that there are qualitative as well as quantitative differences in ErbB family receptor activation by Neuregulin isoforms.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ERBB4 signaling pathway involved_inIDA 151356654PMID:12466964MGI 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
extracellular space is_active_inIDA 151356654PMID:12466964MGI 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
receptor ligand activity enablesIDA 151356654PMID:12466964MGI 

Objects Annotated

Genes (Rattus norvegicus)
Nrg2  (neuregulin 2)


Additional Information