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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase.

The ErbB/HER family of receptor tyrosine kinases consists of four receptors that bind a large number of growth factor ligands sharing an epidermal growth factor- (EGF)-like motif. Whereas ErbB-1 binds seven different ligands whose prototype is EGF, the three families of neuregulins (NRGs) activate ErbB-3 and/or ErbB-4. Here we characterize a fourth neuregulin, NRG-4, that acts through ErbB-4. The predicted pro-NRG-4 is a transmembrane protein carrying a unique EGF-like motif and a short cytoplasmic domain. A synthetic peptide encompassing the full-length EGF-like domain can induce growth of interleukin-dependent cells ectopically expressing ErbB-4, but not cells expressing the other three ErbB proteins or their combinations. Consistent with specificity to ErbB-4, NRG-4 can displace an ErbB-4- bound NRG-1 and can activate signaling downstream of this receptor. Expression of NRG-4 mRNA was detected in the adult pancreas and weakly in muscle; other tissues displayed no detectable NRG-4 mRNA. The primary structure and the pattern of expression of NRG-4, together with the strict specificity of this growth factor to ErbB-4, suggest a physiological role distinct from that of the known ErbB ligands.[1]


  1. Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase. Harari, D., Tzahar, E., Romano, J., Shelly, M., Pierce, J.H., Andrews, G.C., Yarden, Y. Oncogene (1999) [Pubmed]
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