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.

本项目的目的是从小G蛋白Rho家族蛋白和细胞粘附分子发生的细胞内信号事件方面阐明细胞运动的机制。目前，我的项目主要集中在mDia（mammalian Diaphanous）所发生的信号事件，它属于胞质分裂所必需的同源蛋白家族，我在Rho下游发现了两条新的信号通路，Rho-mDia-Src通路（参考文献1）和mDia-DIP-Grb 2通路（参考文献2）。DIP是一种新的mDia相互作用蛋白，广泛表达，具有几个独特的结构域。DIP主要通过其fyn样SH 3结构域与mDia的脯氨酸富集区（FH 1）结合，也通过其脯氨酸富集结构域与Grb 2结合。DIP定位于细胞外周和膜皱褶处，并与mDia共定位。vSrc和DIP的共表达可引起病灶接触区的形态学改变和vSrc的激活，病灶接触区的转换是通过与病灶粘附分子（包括Src和Rho信号相关物质）的协同作用而发生的。因此，我继续研究mDia-Src和DIP途径在焦点接触转换中的作用。

项目成果

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

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

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., 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。

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)