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1999 Fiscal Year Final Research Report Summary

Role of a novel EGF-like molecule containing follistatin modules in the gastrointestinal mucosa

Research Project

Project/Area Number 09470139
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionNippon Medical School

Principal Investigator

SAKAMOTO Choitsu  Nippon Medical School, Third Department of Internal Medicine, Proffessor, 医学部, 教授 (30196092)

Co-Investigator(Kenkyū-buntansha) FUJIMORI Takahiro  Dokkyo University School of Medicine, Department of Pathology, Professor, 医学部, 教授 (30095385)
Project Period (FY) 1997 – 1999
KeywordsEGF / follistatin / stomach fibroblast / tomoregulin (TR) / erbB4 / gastric epithelial cells
Research Abstract

We have isolated a gene from stomach fibroblasts encoding novel proteins containing two follistatin modules which might bind TGF β-related growth factors and a single epidermal growth factor (EGF)-like domain which is closely related to EGF/Neuregulin (NRG) family growth factors. Sequence analysis revealed novel cDNA clones, the protein products of which were designated tomoregulin (TR) and consisted of at least three isoforms which were distinguished by their cytoplasmic domains. The cytoplasmic domains in all isolorms were short and contained potential G-protein activating motifs.
Precursors of TR (Pro-TR) are gloycosylated transmembrance proteins. Two secreted soluble forms resulted from proteolytic cleavage were distinguished by the presence or absence or absence of the EGF-like domain. The EGF-like domain of TR was highly conserved compared to EGF/NRG family growth factors was the exception of an arginine to histidine substitution at position 39 (Arg-> His 39). Soluble TR stimulated erbB-4 tyrosine phosphorylation in MKN 28 gastric cancer cells, although it was weak compared to neuregulin-induced erbB-4 tyrosine phosphrylation ; this suggests that TR might be a ligand for erbB-4 or erbB-4 related receptor tyrosine kinase.
The modular features suggest multiple roles for TR ; these include functioning as a ligand for erbB- receptor, a regulator of TGFβ-related growth factor signaling by direct interaction through the follistatin modules, and a G-protein coupled receptor.

  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Wada K, Sakamoto C, Matsuda K, Uchida T, Noguchi H, et al: "Gastric epithelial cells secrete a PDGF-like peptide, a potent mitogen for human gastric fibroid"Proc.Soc.Exp,Biol.Med.. 217. 109-115 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Noguchi H, Sakamoto C, Wada K, Akamatsu T, Uchida T, et al: "Expression of peregulin α, erbB2 and erbB3 and their influences on proliferation of gastric epithelial cells."Gastroenterology. 117. 1119-1127 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uchida T, Wada K, Akamatsu T, Yonezawa M, et al: "A novel epidermal growth falter like molecule containing two follistatin modules stimulates tyrosine phosphorylation of erbB4"Biochem Biophys Res Commun. 266. 593-602 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada K., Sakamoto C., Matsuda K., Uchida T., Noguchi H, Mizuno H., Akamatsu T., Kasuga M: "Gastric epithelial cells secrete a PDGF-like peptide, a potent mitogen for human gastric fibroblasts."Proc Sos Exp Med.. 217. 109-115 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Noguchi H., Sakamoto C., Wada K., Akamatsu T., Uchida T., Tatsuguchi A, Matsui H., Fukui H, Fujimori T., Kasuga M: "Expession of heregulin α, erbB2, and erbB3 and their influences on proliferation of gastric epithelial cells."Gastoroenterology. 117. 1119-1127 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uchida T., Wada K., Akamatsu T., Yonezawa M., Noguchi H., Mizoguchi A., Kasuga M, C.: "A novel epidermatn growth factor-like molecule containgin two follistatin modules stimulates tyrosine phosphorylation of erbB4 in MKN28 gstric cancer cells."Biochem Bioyhs Res Commun.. 266. 593-602 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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