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p120^<cbl>的功能，这是c-cbl原癌基因在EGF受体刺激后的产物。我们获得了几种稳定表达野生型p120^<cbl>或突变型p120^<cbl>的MDCK细胞系。在这个项目中，我们比较了在p120^<cbl>稳定的转染物中EGF刺激后的信号传递级联。p120^<cbl>是多种细胞中重要的酪氨酸磷酸化底物，p120^<cbl>是体外和体内通过Grb2的氨基末端SH3结构域与Grb2结合的几种底物之一。与Sosl一样，p120^<cbl>具有富含脯氨酸的区域，其中可能包含与SH3结构域结合的基序。然而，p120^<cbl>和Sosl不共免疫沉淀，提示p120^<cbl>-Grb2和Sosl-Grb2是独立的复合物。Grb2-p120^<cbl>相互作用是通过Grb2的氨基末端SH3结构域（N-SH3-Grb2）介导的，我们绘制了与Grb2组成相互作用的p120^<cbl>区域。p120^<cbl>区域位于氨基酸543和548之间。我们还发现，在表达富含脯氨酸（543-548）突变的p120^<cbl>的细胞中，添加EGF后，MAPK的磷酸化显著延长。

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）。