The function of p120^<cbl>, the product of c-cbl protooncogene

c-cbl原癌基因产物p120^<cbl>的功能

• 批准号: 11670443
• 负责人: OTA Yasuo
• 金额: $ 2.18万
• 依托单位: The University of Tokyo
• 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-11670443/
• 关键词: Cbl; Grb2; EGF; MAPK; EGF受容体; 細胞内情報伝達; プロトオンコジンCbl

We tried to elucidate the function of p120^<cbl>, the product of the c-cbl protooncogene after EGF receptor stimulation. We generated several MDCK cell lines which stably express wild type p120^<cbl> or mutant p120^<cbl>. In this project we compared the signal transudation cascades after EGF stimulation in the p120^<cbl> stable transfectants.p120^<cbl> is a prominent tyrosine-phosphorylated substrate in a wide variety of cells_-p120^<cbl> is one of several substrates that binds to Grb2 in vitro and in vivo through the amino-terminal SH3 domain of Grb2. Like Sosl, p120^<cbl> has a proline-rich region that includes likely motifs for binding to SH3 domains. However, p120^<cbl> and Sosl do not coimmunoprecipitate, suggesting that p120^<cbl>-Grb2 and Sosl-Grb2 are separate complexes.The Grb2-p120^<cbl> interaction is mediated through the amino-terminal SH3 domain of Grb2 (N-SH3-Grb2), and we map the region of p120^<cbl> which interacts constitutively with Grb2. This region of p120^<cbl> was found to be between amino acids 543 and 548.We also show that phosphorylation of MAPK is markedly prolonged after addition of EGF in cells which express the proline-rich (543-548) mutated p120^<cbl>.

我们试图阐明原癌基因c-cbl在EGF受体刺激后的产物p120^&lt；cbl&gt；的功能。建立了稳定表达野生型p120；cbl&gt；突变型p120；cbl&gt；野生型p120；在这个项目中，我们比较了p120^&lt；cbl&gt；稳定的转染体中EGF刺激后的信号传导级联。p120^&lt；cbl&gt；是多种细胞中重要的酪氨酸磷酸化底物--p120^&lt；cbl&gt；是在体外和体内通过Grb2的氨基末端SH3结构域与Grb2结合的几种底物之一。和SOSL一样，p120^&lt；CBL&gt；有一个富含脯氨酸的区域，其中包括可能与SH3结构域结合的基序。然而，p120^&lt；CBL&gt；和SOSL没有免疫共沉淀，这表明p120^&lt；CBL&gt；-Grb2和SOSL-Grb2是单独的复合体。Grb2-p120^&lt；cbl&gt；通过Grb2的氨基末端SH3结构域(N-SH3-Grb2)介导相互作用，我们定位了p120^&lt；CBL&gt；cbl&gt；与Grb2结构性相互作用的区域。P120^&lt；cbl&gt；的这一区域位于氨基酸543-548之间。我们还发现，在表达富含脯氨酸(543-548)突变的p120^&lt；cbl&gt；的细胞中，加入EGF后，MAPK的磷酸化明显延长。

项目成果

太田康男: "マコト細胞におけるFcεRI"アレルギー科. 10(1). 8-13 (2000)

Yasuo Ota：“Makoto 细胞中的 FcεRI”，过敏系 10(1)。

太田 康男: "細胞からみたFcεRIの発現調節と機能"アレルギー. 9巻・6号(in press). (2000)

Yasuo Ota：“从细胞角度调节 FcεRI 表达和功能”，第 9 卷，第 6 期（印刷中）。