Clarification of the mechanisms of new signal transductions at the downstram of small GTPase, Rho protein.

阐明小GTP酶、Rho蛋白下游的新信号转导机制。

• 批准号: 12670120
• 负责人: TOMOKO Tominaga
• 金额: $ 2.18万
• 依托单位: Foundation for Advancement of International Science (2001)Dokkyo Medical University (2000)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670120/
• 关键词: Rho; mDia; DIP; Src; cell movement; cell adhesion; 軸索伸長; Grb2

The aim of this project is to clarify the mechanism of cell movement from the aspects of intracellular signaling events occurred by small GTPase Rho family proteins and cell adhesion molecules. Currently, my proposal project is focusing on the signaling events occurred by mDia (mammalian Diaphanous), which belongs to the formin homology protein family essential for cytokinesis.I found two new signal pathways in the downstream of Rho, Rho-mDia-Src pathway (Ref. 1) and mDia-DIP-Grb2 one (Ref. 2). DIP is a new mDia interacting protein which is expressed ubiquitously and has several unique domains. DIP mainly binds to the proline rich region of mDia (FH1) through its fyn-like SH3 domain, and also binds to Grb2 through its proline-rich domain. DIP is localized at the cell periphery and membrane ruffles, and co-localizes with mDia. Co-expression of vSrc and DIP induces significant morphological changes at focal contacts and activation of vSrc.The turnover of focal contacts is occurred by co-ordination with focal adhesion molecules, including Src and Rho signaling-related substances. Therefore, I continue to investigate the role of mDia-Src and DIP pathways in the turnover of focal contacts.

该项目的目的是从细胞内信号事件的各个方面阐明细胞运动的机理，该方面是由小的GTPase Rho家族蛋白和细胞粘附分子发生的。目前，我的建议项目重点是MDIA（哺乳动物多透射）发生的信号事件，该事件属于Cytokinesis必不可少的formin同源性蛋白质家族。 DIP是一种新的MDIA相互作用蛋白，它普遍存在，并具有多个独特的域。浸入主要通过其Fyn样SH3结构域与MDIA富含脯氨酸的区域（FH1）结合，并通过其富含脯氨酸的域与GRB2结合。 DIP位于细胞周围和膜荷叶边，并与MDIA共定位。 VSRC和DIP的共表达在局灶性接触和VSRC激活时引起了显着的形态变化。通过与焦点粘附分子（包括SRC和RHO信号相关物质）协调，局灶性接触的周转率是通过协调而发生的。因此，我继续研究MDIA-SRC和DIP途径在局灶性接触营业额中的作用。

项目成果

Tominaga, T., Sahai, E., Chardin, P., McCormick, F., Courtneidge, SA., Alberts, AS: "Diaphanous -related formines bridge Rho GTPases and Src tyrosine kinase signaling"Mol. Cell. 5. 13-25 (2000)

Tominaga, T.、Sahai, E.、Chardin, P.、McCormick, F.、Courtneidge, SA.、Alberts, AS：“透明相关的甲胺桥接 Rho GTPases 和 Src 酪氨酸激酶信号”Mol。

Numazaki M, Tominaga T, Toyooka H, Tominaga M: "Direct phosphorylation of apsaicin receptor VR1 by PKCε and identification of two target serine residues"Je Biol.Chem.. 277. 13375-13378 (2002)

Numazaki M、Tominaga T、Toyooka H、​​Tominaga M：“PKCε 直接磷酸化 apsaicin 受体 VR1 并鉴定两个目标丝氨酸残基”Je Biol.Chem.. 277. 13375-13378 (2002)

Tominaga T, Sahai E, Chardin P, McCormick.F, Curtneidge A, Alberts S: "Diaphanous-related formines bridge Rho GTPases and Src tyrosine kinase signaling"Mol.Cell.. 5. 13-25 (2000)

Tominaga T、Sahai E、Chardin P、McCormick.F、Curtneidge A、Alberts S：“Diaphanous 相关的甲胺桥 Rho GTPases 和 Src 酪氨酸激酶信号传导”Mol.Cell.. 5. 13-25 (2000)

Satoh S, Tominaga T: "mDia interacting protein acts downstream of Rho-mDia and modifies Src activation and stress fiber formation"Je Biol.Chem.. 276. 39290-39294 (2001)

Satoh S、Tominaga T：“mDia 相互作用蛋白作用于 Rho-mDia 下游并改变 Src 激活和应力纤维形成”Je Biol.Chem.. 276. 39290-39294 (2001)

Tominaga, T., Sahai, E., Chardin, P., McCormick, F., Courtneidge, SA. and Alberts.: "AS Diaphanous-related formines bridge Rho GTPases and Src tyrosine kinase signaling."Mol. Cell.. 5. 13-25 (2000)

Tominaga, T.、Sahai, E.、Chardin, P.、McCormick, F.、Courtneidge, SA。