1996 Fiscal Year Final Research Report Summary
Role of Integrin-mediated Signal Transduction in Cell Growth and Differentiation
| Project/Area Number |
07308047
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 総合 |
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| Research Field |
Structural biochemistry
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| Research Institution | Research Institute, Osaka Medical Center for Maternal and Child Health |
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Principal Investigator |
SEKIGUCHI Kiyotoshi Research Institute, Osaka Medical Center for Maternal and Child Health, Director, 病因病態部門, 部長 (50187845)
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| 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)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Integrin / Extracellular Matrix / Cell Adhesion / PAxillin / Cadherin / Smooth Moscle Cells / Laminin / Membrane-bound Cell Growth Factor |
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| 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.
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