A novel brain-derived member of the epidermal growth factor family that interacts with ErbB3 and ErbB4

Shigeki Higashiyama, Michiharu Horikawa, Kouji Yamada, Naohiro Ichino, Norihiko Nakano, Takatoshi Nakagawa, Junichiro Miyagawa, Natsuki Matsushita, Toshiharu Nagatsu, Naoyuki Taniguchi, Hiroshi Ishiguro

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A novel member of the epidermal growth factor (EGF) family, the neural- and thymus-derived activator for ErbB kinases (NTAK), has been purified and cloned. Five alternative spliced isoforms have been detected in the rat adrenal pheochromocytoma cell line, PC-12 cells. The rat NTAK(α)2a isoform exhibits 94% identity in its primary sequence with the human NTAK(α) isoform. In vivo, NTAK is only expressed in the brain of rat E11.5 embryos, and in the brain and thymus of adult rats. The soluble 46 kDa form binds directly to ErbB3 and B4, but not to ErbB1 or B2. NTAK, however, transactivates ErbB1 and B2 via heterodimerization with ErbB3 or B4. NTAK stimulates the differentiation of MDA-MB-453 cells and competitively inhibits the binding of [125I]neuregulin to these cells. In addition to these neuregulin-like properties, NTAK exhibits limited structural homology to neuregulins in the immunoglobulin (Ig)-like, EGF-like, and hydrophobic domains. Thus, NTAK appears to be a new member of the EGF family displaying neuregulin properties.

Original languageEnglish
Pages (from-to)675-680
Number of pages6
JournalJournal of Biochemistry
Issue number3
Publication statusPublished - 09-1997


All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Higashiyama, S., Horikawa, M., Yamada, K., Ichino, N., Nakano, N., Nakagawa, T., Miyagawa, J., Matsushita, N., Nagatsu, T., Taniguchi, N., & Ishiguro, H. (1997). A novel brain-derived member of the epidermal growth factor family that interacts with ErbB3 and ErbB4. Journal of Biochemistry, 122(3), 675-680. https://doi.org/10.1093/oxfordjournals.jbchem.a021806