The PDZ protein TIP-1 interacts with the Rho effector rhotekin and is involved in Rho signaling to the serum response element

作     者：Reynaud, C Fabre, S Jalinot, P 

作者机构：Ecole Normale Super Lyon CNRS UMR 5665 Lab Biol Mol & Cellulaire F-69364 Lyon 07 France 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：2000年第275卷第43期

页      面：33962-33968页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

主　　题：氨基酸序列 COS细胞 载体蛋白质类/生理学 克隆 分子 DNA结合蛋白质类/生理学 基因表达调控 谷氨酰胺酶 HeLa细胞 细胞内信号肽和蛋白质类 Lim激酶类 分子序列数据 蛋白激酶类 蛋白质丝氨酸苏氨酸激酶/生理学 蛋白质类/遗传学 蛋白质类/生理学 反应元件 ρAGTP结合蛋白质/生理学 动物 人类 

摘      要：The human T-cell lymphotrophic virus, type 1 Tax protein can interact via its C terminus with various proteins including a PDZ domain. In this work, one of them, TIP-1, is characterized as a cytoplasmic 14-kDa protein mainly corresponding to one PDZ domain. A two-hybrid screen performed with TIP-1 as bait showed that it interacts with the human homologue of rhotekin that was previously identified in mice as a Rho effector. Both human and mouse rhotekins exhibit at their C termini the sequence QSPV-COOH that matches the X(S/T)XV-COOH consensus known for proteins recognizing PDZ domains. Mutation of the serine and valine residues to alanine impairs interaction of rhotekin with TIP-I. Transient expression experiments with a reporter construct including the c-Fos serum response element (SRE) showed that coexpression of TIP-I with the constitutively active RhoA.V14 mutant and human rhotekin caused a strong activation of the SRE. A negative mutant of Rho, RhoA.N19, was unable to cooperate with TIP-1 and rhotekin, The positive effect of TIP-I was also lost when the C terminus of rhotekin was mutated. These data show that the complex of active Rho with its effector rhotekin bound to TIP-1 produces in the cytoplasm a signal that triggers strong activation of the SRE.