Research for physiological roles of protein tyrosine phosphatases for cell adhesion.

研究蛋白质酪氨酸磷酸酶对细胞粘附的生理作用。

基本信息

批准号：
11670121
负责人：
MATOZAKI Takashi
金额：
$ 2.43万
依托单位：
Gunma University (2000)Osaka University (1999)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670121/
关键词：
Protein tyrosine phosphatase SAP-1 SHP-2 PTPH1 Tyrosine phosphorylation Cell adhesion Ezrin PDZ domain 細胞運動

项目摘要

It has been suggested that tyrosine phosphorylation or dephosphorylation of proteins localized at cell-cell junctions plays an important role in the regulation of cell adhesion functions. We have been studying physiological roles of protein tyrosine phosphatases (PTPases) and discovered novel PTPases, such as SAP-1, SHP-2, and PTPH1. SAP-1 is a receptor-like PTPase, while SHP-2 is a non-transmembrane-type PTPase containing two SH2 domains. PTPH1 is also a non-transmembrane-type PTPase that contains an Ezrin-like structure and a PDZ domain in its N-terminal region. Thus, all these PTPases could be involved in the regulation of cell adhesion. In this study, we investigated the physiological roles of these three PTPases. The results obtained are follows :(1) Integrin-based cell adhesion directly regulates the catalytic activity of SAP-1. Expression of SAP-1 inhibits cell proliferation presumably through dephosphorylation of p130cas and other proteins localized at integrin-based cell adhesion sites. This inhibitory effect of SAP-1 may be related to "contact inhibition".(2) SHP-2 physiologically suppresses the activity of Rho and it thereby positively regulates the HGF/SF-induced cell scattering. In addition, Vav2 may be involved in the SHP-2-Rho pathway. We have generated knockout mice of SHPS-1, an SHP-2 substrate, and have shown that SHPS-1 is essential for the regulation of Ras and Rho.(3) We have tried to identify the proteins bound to the Ezrin domain or the PDZ domain of PTPH1 by the yeast two-hybrid system. We will analyze the function of these binding partners of PTPH1.

有人提出，位于细胞-细胞连接处的蛋白质的酪氨酸磷酸化或去磷酸化在细胞粘附功能的调节中发挥重要作用。我们一直在研究蛋白酪氨酸磷酸酶 (PTPases) 的生理作用，并发现了新型 PTPase，例如 SAP-1、SHP-2 和 PTPH1。 SAP-1是一种受体样PTPase，而SHP-2是一种包含两个SH2结构域的非跨膜型PTPase。 PTPH1也是一种非跨膜型PTPase，其N端区域包含Ezrin样结构和PDZ结构域。因此，所有这些 PTPase 都可能参与细胞粘附的调节。在本研究中，我们研究了这三种 PTPase 的生理作用。所得结果如下：(1)基于整合素的细胞粘附直接调节SAP-1的催化活性。 SAP-1 的表达可能通过 p130cas 和位于基于整合素的细胞粘附位点的其他蛋白质的去磷酸化来抑制细胞增殖。 SAP-1的这种抑制作用可能与“接触抑制”有关。(2)SHP-2在生理上抑制Rho的活性，从而正向调节HGF/SF诱导的细胞散射。此外，Vav2可能参与SHP-2-Rho途径。我们已经培育出 SHPS-1（一种 SHP-2 底物）的敲除小鼠，并表明 SHPS-1 对于 Ras 和 Rho 的调节至关重要。(3) 我们尝试鉴定与 Ezrin 结构域或 Ezrin 结构域结合的蛋白质。酵母双杂交系统的 PTPH1 的 PDZ 结构域。我们将分析 PTPH1 的这些结合伙伴的功能。