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Regulation of TGF-b and Wnt signal interaction

Research Project

Project/Area Number 12480218
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionTokyo Dental and Medical University

Principal Investigator

SHIBUUYA Hiroshi  Tokyo Dental and Medical University, Professor, 難治疾患研究所, 教授 (30261324)

Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2001: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 2000: ¥7,600,000 (Direct Cost: ¥7,600,000)
KeywordsTGF-b / BRAM / BIP / C. elegans / BRA-1,2 / daf / sma / RNAi / TGF-β / BRA-1, 2 / オーガナイザー形成 / Wntシグナル / Xtwn / Smad4 / LEF1 / β-catenin / 複合体形成
Research Abstract

The TGF-b superfamily has diverse biological activities and is involved in the early devel opment of animals. We previously identified a novel family member, BMP receptor associated molecule (BRAM), which binds to the intracellular domain of BMP type IA receptor and is involved in the BMP signaling pathway.
To identify novel molecules involved in TGF-b signaling pathways, we performed yeast two-hybrid screening using BRAM as bait. From a Xenopus cDNA library, we cloned a cDNA encoding 693 amino acids and containing an oxysterol binding protein (OSBP) motif, which we designated BRAM interacting protein (BIP). We then isolated a BIP homologue from the C. elegans that encodes 733 amino acids and also contains the OSBP-like motif. Immunoprecipitation and Western blotting studies revealed that C. elegans BIP could interact with the C. elegans BRAM homologues, BRA-1 and BRA-2. C. elegans BIP was expressed in pharyngeal muscle, hypodermis and several neuronal cells, an expression pattern overlaps with those of BRA-1 and BRA-2. Finally, we found that inhibition of BIP expression in C. elegans by double stranded RNA interference produces a Sma phenotype.
BIP was isolated using the yeast two-hybrid systems. BIP may function in TGF-b pathway and regulate body length in C. elegans.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Masuda et al.: "Dlxin, a novel protein that binds Dlx5 and regulates its transcriptional function"J. Biol. Chem.. 276. 5331-5338 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohnishi et al.: "Cloning and characterization of a rat ortholog of MMP-23 (Matrix metalloproteinase-23), a unique type of membrane-anchored matrix metalloproteinase and conditioned switching of its expression during the ovarian follicular"Mol. Endocrinol.. 15. 747-764 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Morita et al.: "A DAF-1-binding protein BRA-I is a negative regulator of DAF-7 TGF-b signaling"Proc. Natl. Acad. Sci. USA. 98. 6284-6288 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugawara et al.: "BIP, a BRAM-interacting protein involved in TGF-b signaling, regulates body length in C.elegans"Genes Cells. 6. 599-606 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shirakabe et al.: "Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5"Genes Cells. 6. 1091-1099 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hyodo-Miura et al.: "Involvement of NLK and Sox11 in neural induction in Xenopus development"Genes Cells. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masuda, Y., Sasaki, A., Shibuya, H., Ueno, N., Ikeda, K. and Watanabe, K.: "Dlxin, a novel protein that binds Dlx5 and regulates its tran scriptional function"J. Biol. Chem.. 276. 5331-5338 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohnishi, J., Ohnishi, E., Jin, M., Hirano, W., Nakane, D., Matsui, H., Kimura, A., Sawa, H., Nakayama, K., Shibuya, H., Nagashima, K. and Takahashi, T.: "Cloning and characterization of a rat ortholog of MMP-23 (Matrix metalloproteinase-23), a unique type of membrane-anchored matrix metalloproteinase and conditioned switching of its expression during the ovarian follicular development"Mol. Endocrinol.. 15. 747-764 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Morita, K., Shimizu, M., Shibuya, H. and Ueno, N.: "A DAF-1-binding protein BRA-1 is a negative regulator of DAF-7 TGF-b signaling"Proc. Natl. Acad. Sci. USA 98. 6284-6288 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugawara, K., Morita, K., Ueno, N. and Shibuya, H.: "BIP, a BRAM-interacting protein involved in TGF-b signaling, regulates body length in C. elegans"Genes Cells. 6. 599-606 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shirakabe, K., Terasawa, K., Miyama, K., Shibuya, H. and Nishida, E.: "Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5"Genes Cells. 6. 851-856 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hyodo-Miura, J., Urushiyama, S., Nagai, S., Nishita, M., Ueno N. and Shibuya, H.: "Involvement of NLK and Sox11 in neural induction in Xenopus development"Genes Cells. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masuda, Y. et al.: "Dixin, a novel protein that binds Dlx5 and regulates its transcriptional function"J. Biol. Chem.. 276. 5331-5338 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohnishi, J. et al.: "Cloning and characterization of a rat orthlog ofMMP-23 (Matrix metalloproteinase-23) a unique type of membrane-anchored matrix metalloproteinase and conditioned switching of its expression during the overian follicular development"Mol. Endocrinol.. 15. 747-764 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Morita, K. et al.: "A DAF-1-binding protein BRA-1 is a negative regulator of DAF-7 TGF-β signaling"Proc. NatL. Acad. Sci. USA. 98. 6284-6588 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugawara, K. et al.: "BIP, a BRAM-interacting protein involved in TGF-β signaling, regulates body length in C.elegans"Genes Cells. 6. 599-606 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shirakabe, K. et al.: "Regulation of the activity of the transcription factor Runx2 by two homeobox_proteins, Msx2 and Dlx5"Genes Cells. 6. 851-856 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hyodo-Miura, J. et al.: "Involvement of NLK and Sox11 in neural induction in Xenopus development"Genes Cells. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nishita,M.et al.: "Smad8B, a Smad8 splice variant lacking the SSXS site that inhibits Smad8-mediated signaling."Nature. 403. 781-785 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takatsu,Y.et al.: "TAK1 participates in c-Jun N-terminal kinase signaling during Drosophila development."Mol.Cell.Biol.. 20. 3015-3026 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takaesu,G.et al.: "TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal trunsduction pathway."Mol.Cell. 5. 649-658 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kimura,N.et al.: "BMP2-induced apoptosis is mediated by activation of TAK1-p38 kinase pathway that is negatively regulated by Smad6."J.Biol.Chem.. 275. 17647-17652 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tago,K.et al.: "Inihibition of Wntsignaling by ICAT, a novel β-catenin-interacting protein."Genes Dev.. 14. 1741-1749 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hanafusa,H.et al.: "The TGF-β family member derriere is involved in regulation of the establishment of left-right asymmetry."EMBO Rep.. 1. 32-39 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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