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Role of Integrin-mediated Signal Transduction in Cell Growth and Differentiation

Research Project

Project/Area Number 07308047
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section総合
Research Field Structural biochemistry
Research InstitutionResearch Institute, Osaka Medical Center for Maternal and Child Health

Principal Investigator

SEKIGUCHI Kiyotoshi  Research Institute, Osaka Medical Center for Maternal and Child Health, Director, 病因病態部門, 部長 (50187845)

Co-Investigator(Kenkyū-buntansha) MEKADA Eisuke  Institute of Life Science, Kurume University, Professor, 分子生命科学研究所, 教授 (20135742)
MIYAZAKI Kaoru  Kihara Institute for Biological Research, Yokohama City University, Professor, 木原生物学研究所, 教授 (70112068)
SOBUE Kenji  Osaka University Faculty of Medicine, 医学部, 教授 (20112047)
SABE Hisataka  Institute for Virus Institute, Kyoto University, Associate Professor, ウイルス研究所, 助教授 (40187282)
OZAWA Masayuki  Kagoshima University Facluty of Medicine, Professor, 医学部, 教授 (90136854)
NARUMIYA Shuh  Kyoto University Faculty of Medicine, Professor (70144350)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 1996: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1995: ¥6,100,000 (Direct Cost: ¥6,100,000)
KeywordsIntegrin / Extracellular Matrix / Cell Adhesion / PAxillin / Cadherin / Smooth Moscle Cells / Laminin / Membrane-bound Cell Growth Factor / シグナル伝達 / 細胞内骨格系 / Rho / HB-EGF
Research Abstract

(1) Alternative splicing of the fibronectin pre-nRNA at the EDA region was found to regulate the cell-adhesive and integrin alpha5beta1 binding activities of fibronectin. This is the first evidence for the regulation of the integrin-mediated signal transduction by alternative splicing of the extracellular matrix components. (2) The integrin alpha3beta1 binding on laminin-5 was localized in the G2 domain using a series of bacterially produced recombinant fragments derived from different domains of laminin-5. (3) Novel isoforms of paxillin, a crucial adaptor molecule associated with integrins and cytoskeletons, were identified. One of the isoforms, designated paxillin gamma, was found to lack the ability to bind vinculin. (4) Importance of the heparin-binding fomain of HB-EGF,a membrane-bound cell growth factor, in its association with the cell surface EGF receptors was demonstrated, being consistent with the previous findings that cell surface heparan sulfate proteoglycans were involved in the binding of HB-EGF with EGF receptors. (5) Laminin-1 and IGF-1 (insulin-like growth factor-1) were found to be key factors in the maintenance of differentiated phenotypes of smooth muscle cells. (6) Mouse L cells transfected with E-cadherin cDNA were found to be more adhesive onto the substrates, particularly those coated with collagen type IV.Overexpression of E-cadherin was also found to suppress the growth of leukemic cells.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Tsutsui,J.,et al.: "Expression of cadherin-catenin complexes in human leukemia cell lines" J.Biochem.120. 1034-1039 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Pu,et al.: "CD 45 medulates plesphorylation of both authephosphorlation and negative regulatory tyrosines of lyn in B cells." J.Biol.Chem.271. 30487-30492 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka,T.et al.: "Paxillin association in vitro with integrin cyto-phasmic demain peptides." FEBS Lett.399. 53-58 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Chen,J.et al.: "Distinct structural reguirments for interaction of the Integrins α5β1 αγβ5 and αγβ6 with the central cell binding domain" Cell Adh.Commun. 4. 237-250 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ishikawa,T.et al.: "Matrebysin is associated with progression of colorectal tumor." Cancer.Lett.107. 5-10 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakamura,Y.et al.: "Expression and distribution of CD9 in nyelin of the central and perepheral nerous systems." Am.J.Pathol.149. 575-583 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 小澤政之: "カドヘリン・カテニン複合体とシグナリング" 実験医学, 6 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 関口清俊: "バイオサイエンス用語ライブラリー・細胞接着 フィグロネクチン" 羊土社(宮坂昌之・矢原一郎 編), 2 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamamoto, H., A.Irie, Y.Fukushima, T.Ohnishi, N.Arita, T.Hayakawa, and K.sekiguchi: "Abrogation of lung metastasis of human fibrosarcoma cells by ribozyme-mediated suppression of integrin alpha6 subunit expression" Int. J.Cancer. 65. 519-524 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Murayama, O., H.Nishida, and K.Sekiguchi: "NOvel peptide lignds for integrin alpha6beta1 selected from a phase display library" J.Biochem.120. 445-451 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akamatsu, H., K.Ichihara-Tanaka, K.Ozono, W.Kamiike, H.Matsuda, and K.Sekiguchi: "suppression of transformed phenotypes of human fibrosarcoma cells by overexpression of recombinant fibronectin" Cancer Res.56. 4541-4546 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Chen, J., T.Maeda, K.Sekiguchu, and D.Sheppard: "Distinct structural requirements for interaction of the integrin alpha5beta1, alphavbeta6, and alphavbeta6 with the central cell binding domain in fibronectin" Cell Adh. Commun.4. 237-250 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka, T., R.Yamaguchi, H.Sabe, K.Sekiguchi, and J.M.Healy: "Paxillin association in vitro with integrin cytoplasmic domain peptides" FEBS lett.399. 53-58 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kikkawa, Y., K.Akagoi, H.Mizushima, N.Yamanaka, M.Umeda, and K.Miyazaki: "Stimulation of endothelial cell migration in culture by ladsin, a alaminin-5-like cell adhesion protein" In Vitro Cell. dev. Biol.32. 46-52 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akagoi, K., Y.Okabe, J.Sato, Y.Nagashima, H.Yasumiysu, K.Sugawara, and K.Miyazaki: "Specific accumulation of tumor-derived adhesion factor in tumor blood vessels and in capillary tube-like structures of cultures vascular endothelial cells" Proc. Natl. Acad. Sci. USA. 93. 8384-8389 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mizushima, H., Y.Miyagi, Y.Kikkawa, N.Yamanaka, H.Yasumitsu, K.Misugi, and K.Miyazaki: "differentioal expression of laminin-5/ladsin subunits in human tissues and cancer cell lines and their induction by tumor promotor and growth factors" J.Biochem.120. 1196-1202 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakamura, Y., R.Iwamoto, and E.Mekada: "Expression and distribution of CD9 in myelin of the central and peripheral nervous systems" Am. J.Pathol.149. 575-583 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Obata, H., K.Hayashi, W.Nishida, T.Momiyama, and K.Sobue: "Smooth muscle cell phenotype-dependent transcriptional regulation of the alpha1 integrin gene" J.Biol. Chem.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sabe, H., M.Hamaguchi, and H.Hanafusa: "Cell to substratum sdhesion is involved in v-Src induced protein tyrosine phosphorylation : implication for the adhesion-regulated protein tyrosine phosphatase activity" Oncogene. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mazaki, Y., S.Hashimoto, and H.Sabe: "Monocyte cells and cancer cells express novel paxillin isoforms with different binding properties to focal adhesion proteins" J.Biol. Chem.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsutsui,J.,et al.: "Expression of cadherin-catenin complexes in human leukemia cell lines." J.Biochem.120. 1034-1039 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Pu,et al.: "CD45 modulates phosphorylation of both autophosphorylation and negrtive regulatory tyrasines of Lyn in B cells." J.Biol.Chem.271. 30487-30492 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,T.et al.: "Paxillin association in vitro with integrin cytoplasmic domain peptides." FEBS Lett.399. 53-58 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Chen,J.et al.: "Distiuct structural requirements for interaction of the integrins α5A1,αVβ5、and αVβ6 with the central cell binding domain in fibrorectin." Cell Adh.Commun.4. 237-250 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ishikawa,T.,et al.: "Matrilysin is associated with progression of colorectal tumor." Cancer.Lett.107. 5-10 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakamura,Y.,et al.: "Expression and distribition of CD9 in myelin of the central and perepheral mervous systems." Am.J.Pathol.149. 575-583 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 小澤政之: "カドヘリン・カテニン複合体とシグナリング" 実験医学, 6 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 関口清俊(宮坂昌之・矢原一郎編): "バイオサイエンス用語ライブラリー;細胞接着 フィブロネクチン" 羊土社, 2 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohashi, H., et al.: "Up-regulation of α5β1 expression by interleukin-6 in rabbit corneal epithelial cells." Experimental Cell Research. 218. 418-423 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fukai, F., et al.: "Release of biological activities from quiescent fibronectin molecule by conformational change and limited proteolysis by matrix metalloproteinases." Biochemistry. 34. 11453-11459 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Watanabe, G., et al.: "Protein kinase N(PKN) and PKN-related protein rhophilin as targets of small GTPase Rho." Science. 271. 645-648 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakamura, K., et al.: "Membrane anchored hepalin-binding EGF-like growth factor and DRAP27/CD9 from a complex with integrin α3β1 at cell-cell contact sites." The Journal of Cell Biology. 129. 1691-1705 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sabe, H., et al.: "Possible v-Crk-induced Transformation through Activation of Src Kinases." The Journal of Biological Chemistry. 270. 31219-31224 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yano, H., et al.: "Transacriptional regulation of chicken caldesmon gene: activation of gizzard type caldesmon promoter a CArG box-like motif." The Journal of Biological Chemistry. 270. 23661-23666 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mekada, E.: "Handbook of natural toxins: Bacterial toxins and virulence factors in disease." Marcel Dekker Inc., 95-109 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tominaga, T., et al.: "Methods in Enzymology, Volume256" Academic Press Inc., 290-297 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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