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Mechanisms of basement membrane recognition by cell with special reference to cell adhesion-dependent signal transduction

Mechanisms of basement membrane recognition by cell with special reference to cell adhesion-dependent signal transduction
细胞识别基底膜的机制,特别是细胞粘附依赖性信号转导
批准号:
18370044
负责人:
SEKIGUCHI Kiyotoshi
金额:
$11.03万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2006
资助国家:
日本
项目状态:
已结题
起止时间:
2006 至 2007

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项目成果

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中文摘要
翻译
层粘连蛋白的单个亚基链(即α链、β链和γ链)在层粘连蛋白结合整合素中的作用已被研究。我们证明了gamma1和gamma2链的c端区域,特别是位于c端第三位的Glu残基,在层粘连蛋白的整合素识别中起着关键作用。因此,Glu残基的删除或Glu残基的Gln取代了含有gamma1或gamma2链的层粘连蛋白异构体的整合素结合活性。为了进一步证明Glu残基在gamma1和gamma2链中的重要性,我们还证明了gamma3链比其他gamma链短且缺乏Glu残基,在与认知整合素的结合中存在缺陷。我们还发现β链的c端区域,特别是c端22个氨基酸残基,参与调节层粘连蛋白的整合素结合亲和力。因此,含有beta2链的同工异构体比含有beta1链的同工异构体更能与认知整合素(如alpha3beta1)结合。这些结果表明β链和γ链的c端区域都参与了层粘连蛋白对整合素的结合。我们也证明了在八种rgd结合的整合素中,alpha8beta1特异性地与nephronectin结合。
英文摘要
Roles of individual subunit chains of laminins (i.e., alpha, beta and gamma chains) in integrin binding by laminins have been investigated. We demonstrated that the C-terminal region of the gamma1 and gamma2 chains, particularly the Glu residue at the third position from their C-termini, was critically involved in integrin recognition of laminins. Thus, the deletion of the Glu residue or the substitution of a Gln for the Glu residue abrogated the integrin binding activity of laminin isoforms containing either gamma1 or gamma2 chains. To extend the importance of the Glu residue within the gamma1 and gamma2 chains, we also demonstrated that the gamma3 chain that is shorter than other gamma chains and lacks the Glu residue was defective in binding to cognitive integrins. We also found that the C-terminal regions of the beta chains, particularly the C-terminal 22 amino acid residues, were involved in modulation of integrin binding affinities of laminins. Thus, the isoforms containing the beta2 chain was more potent than those containing the beta1 chain in binding to cognitive integrins, e.g., alpha3beta1. These results indicate that the C-terminal regions of both beta and gamma chains participate in the integrin binding by laminins. We also demonstrated that among the eight RGD-binding integrins, alpha8beta1 bound specifically to nephronectin.
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会议论文
The requirement of the glutamic acid residue at the third position from the carboxyl termini of the laminin Y chains in integrin binding by laminins
层粘连蛋白与整合素结合时层粘连蛋白 Y 链羧基末端第三位谷氨酸残基的要求
DOI: --
发表时间: 2007
期刊: J. Biol. Chem 282
影响因子: --
作者: [Ido, H., Nakamura, A., Kobayashi, R., Ito, S., Li, S., Futaki, S., Sekiguchi]
通讯作者: Sekiguchi
再生医療のための細胞生物学
再生医学的细胞生物学
DOI: --
发表时间: 2007
期刊:
影响因子: --
作者: [眞鍋理一郎, 関口清俊, 金井好克, Okada S, 関口 清俊]
通讯作者: 関口 清俊
DOI: 10.1074/jbc.m609402200
发表时间: 2007-04-13
期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
影响因子: 4.8
作者: [Ido, Hiroyuki, Nakamura, Aya, Sekiguchi, Kiyotoshi]
通讯作者: Sekiguchi, Kiyotoshi
Diversity and specificity of the adhesive interactions of cells with the basement membrane
细胞与基底膜粘附相互作用的多样性和特异性
DOI: --
发表时间: 2007
期刊:
影响因子: --
作者: [Sekiguchi, K]
通讯作者: K
共 15 条
    Molecular mechanisms of basement membrane recognition by integrins
    • 批准号:
      20370046
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $12.9万
    • 财政年份:
      2008
    • 负责人:
      SEKIGUCHI Kiyotoshi
    • 依托单位:
    Customization and cellular recognition of the extracellular matrix
    • 批准号:
      17082005
    • 项目类别:
      Grant-in-Aid for Scientific Research on Priority Areas
    • 资助金额:
      $41.6万
    • 财政年份:
      2005
    • 负责人:
      SEKIGUCHI Kiyotoshi
    • 依托单位:
    Regulatory mechanisms of ligand binding and signaling events of laminin-binding integrins
    • 批准号:
      15370055
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $9.47万
    • 财政年份:
      2003
    • 负责人:
      SEKIGUCHI Kiyotoshi
    • 依托单位:
    Studies on the Regulatory Mechanisms and Molecular Diversity of Integrinmediated Signal Transduction
    • 批准号:
      12480189
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $7.74万
    • 财政年份:
      2000
    • 负责人:
      SEKIGUCHI Kiyotoshi
    • 依托单位:
    海外基金