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

整合素介导的信号转导在细胞生长和分化中的作用

基本信息

批准号：
07308047
负责人：
SEKIGUCHI Kiyotoshi
金额：
$ 7.1万
依托单位：
Research Institute, Osaka Medical Center for Maternal and Child Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07308047/
关键词：
Integrin 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

项目摘要

(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.

(1)在EDA区域的纤连蛋白前体nRNA的选择性剪接被发现调节纤连蛋白的细胞粘附和整合素α 5 β 1结合活性。这是第一个证据的整合素介导的信号转导的细胞外基质成分的选择性剪接的调节。(2)整合素α 3 β 1结合层粘连蛋白5被定位在G2域使用一系列细菌产生的重组片段，来自不同的结构域的层粘连蛋白5。(3)桩蛋白是一种与整联蛋白和细胞骨架相关的重要衔接分子，它的新型亚型被鉴定出来。其中一种亚型，称为桩蛋白γ，被发现缺乏结合黏着斑蛋白的能力。(4)HB-EGF是一种膜结合细胞生长因子，其肝素结合形式在与细胞表面EGF受体结合中的重要性得到证实，这与以前的发现一致，即细胞表面硫酸乙酰肝素蛋白聚糖参与HB-EGF与EGF受体的结合。(5)层粘连蛋白-1和IGF-1（胰岛素样生长因子-1）被认为是维持平滑肌细胞分化表型的关键因素。(6)研究发现，用E-钙粘蛋白cDNA转染的小鼠L细胞对基质的粘附性更强，特别是那些涂有IV型胶原蛋白的基质。还发现E-钙粘蛋白的过表达可以抑制白血病细胞的生长。