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Characterization of a novel ligand for Receptor Tyrosine Kinase ErbB

Research Project

Project/Area Number 09680620
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionOsaka University

Principal Investigator

HIGASHIYAMA Shigeki  Osaka University Medical School, Assistant Professo, 医学部, 助手 (60202272)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥3,400,000 (Direct Cost: ¥3,400,000)
KeywordsErbB tyrosine kinase / Cell growth / Cell differentiation / neuregulin / NTAK / ErbB チロシンキナーゼ / EGF ファミリー / Neuregulin
Research Abstract

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 (alpha1, alpha 2 a alpha2b, beta, gamma) have been detected in the rat adrenal pheochromocytoma cell line, PC-12 cells.The rat NTAKalpha2a isoform exhibits 94% identity in its primary sequence with the human NTAKalpha 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.NTA,K except gamma-isofrom, 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.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Ouchi,N.: "Role of membrane-anchored heparin-binding epidermal growth factor-like growth factor and CD9 on macrophages." Biochem.J.328. 923-928 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hayase,Y.: "Neuronal and glial expression of heparin-binding EGF-like growth factor in rat brains." Brain Res.784. 163-178 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yokosaki,Y.: "Identification of the ligand binding site for the integrin α9β1 in the third fibronectin tvpe III repeat of tenascin-C." J.Biol.Chem.273. 11423-11428 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada,A.: "Plasma heparin-binding EGF-like growth factor levels in patients afterpartial hepatectomy as determined with an enzyme-linked immunosorbent assay." Biochem.Biophys.Res.Commun.246. 783-787 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miyazaki,Y.: "Gastrin induces heparin-binding epidermal growth factor-like growth factor in rat gastric epithelial cells transfected with gastrin receptor." Gastroenterology. 116. 78-89 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ouchi, N., Hihara, S., Yamashita, S., Higashiyama, S., Nakagawa, T., Shinomura, I., Funahashi, T., Kameda-Takemura, K., Kawata, S., Taniguchi, N., and Matsuzawa, Y.: "Role of membrane-anchored heparin-binding epidermal growth factor-like growth factor and CD9 on macrophages." Biochem.J.328. 923-928 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hayase, Y., Sasahara, M., Nakagawa, T., Higashiyama, S., Taniguchi, N., Amano, S., Hazama, F.: "Neuronal and glial expression of heparin-binding EGF-like growth factor in rat brains." Brain Res.784. 163-178 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yokosaki, Y., Matsuura, N., Higashiyama, S., Murakami I., Obara, M., Yamakido, M., Shigeto, N., Chen, J., Sheppard, D.: "Identification of the ligand binding site for the integrin alpha9beta1 in the third fibronectin type III repeat of tenascin-C." J.Biol.Chem.273. 11423-11428 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada, A., Kawata, S., Tamura, S., Kiso, S., Higashiyama, S., Umeshita, K., Sakon, M., Taniguchi, N., Monden, M., and Matsuzawa, Y.: "Plasma heparin-binding EGF-like growth factor levels in patients afterpartial hepatectomy as determined with an enzyme-linked immunosorbent assay." Biochem.Biophys.Res.Commun. 246. 783-787 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miyazaki, Y., Shinomura, Y., Tsutsui, S., Zushi, S., Higashimoto, Y., Kanayama, S., Higashiyama, S., Taniguchi, N., and Matsuzawa, Y.: "Gastrin induces heparin-binding epidermal growth factor-like growth factor in rat gastric epithelial cells transfected with gastrin receptor." Gastroenterology. 116. 78-89 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ouchi,N.: "Role of membrane-anchored heparin-binding epidermal growth factor-like growth factor and CD9 on macrophages." Biochem.J.328. 923-928 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayase,Y.: "Neuronal and glial expression of heparin-binding EGF-like growth factor in rat brains." Brain Res.784. 163-178 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yokosaki,Y.: "Identification of the ligand binding site for the integrin α9β1 in the third fibronectin type III repeat of tenascin-C." J.Biol.Chem.273. 11423-11428 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamada,A.: "Plasma Heparin-binding EGF-like growth factor levels in patients afterpartial hepatectomy as determined with an enzyme-linked immunosorbent assay." Biochem.Biophys.Res.Commun.246. 783-787 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyazaki,Y.: "Gastrin induces heparin-binding epidermal growth factor-like growth factor in rat gastric epithelial cells transfected with gastrin receptor" Gastronterology. 116. 78-89 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishi,E.: "Lysophosphatidylcholine increases expression of hwparin-binding epidermal growth factor-like growth factor in human T-lymphocytes" Circ.Res.80. 638-644 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyoshi,E.: "Membrane anchored heparin-binding EGF-like growth factor acts as a tumor survival factor in hepatoma cell lines" J.Biol.Chem.272. 14349-14355 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Che,W.: "Selelctive Induction of heparin-binding EGF-like growth factor by methylglyoxal and 3-deoxyglucosone in rat aortic smooth muscle cells" J.Biol.Chem.272. 18453-18459 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Inui,S.: "Growth of cultured normal human keratinocytes is mediated by membrane anchored heparin-binding EGF-like growth factor and amphiregulin in associated with CD9" J.Cell.Physiol.171. 291-298 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Higashiyama,S.: "A novel brain-derived member of the EGF family that interacts with ErbB3 and ErbB4" J.Biochem.122. 675-680 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kaneto,H.: "Expression of HB-EGF during pancreas development : a potential role of PDX-1 in the transcreptional activation" J.Biol.272. 29137-29143 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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