TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4

被引：910
|
作者：
Nakao, A
Imamura, T
Souchelnytskyi, S
Kawabata, M
Ishisaki, A
Oeda, E
Tamaki, K
Hanai, J
Heldin, CH
Miyazono, K
tenDijke, P
机构：
[1] JAPANESE FDN CANC RES,INST CANC,DEPT BIOCHEM,TOSHIMA KU,TOKYO 170,JAPAN
[2] JAPAN SOC PROMOT SCI,RES FUTURE PROGRAM,TOSHIMA KU,TOKYO 170,JAPAN
来源：
EMBO JOURNAL | 1997年 / 16卷 / 17期
关键词：
nuclear translocation; phosphorylation; signal transduction; transforming growth factor-beta;
D O I：
10.1093/emboj/16.17.5353
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Smad family members are newly identified essential intracellular signalling components of the transforming growth factor-beta (TGF-beta) superfamily, Smad2 and Smad3 are structurally highly similar and mediate TGF-beta signals, Smad4 is distantly related to Smads 2 and 3, and forms a heteromeric complex with Smad2 after TGF-beta or activin stimulation, Here we show that Smad2 and Smad3 interacted with the kinase-deficient TGF-beta type I receptor (TPR)-I after it was phosphorylated by TPR-II kinase, TGF-beta 1 induced phosphorylation of Smad2 and Smad3 in Mv1Lu mink lung epithelial cells, Smad4 was found to be constitutively phosphorylated in Mv1Lu cells, the phosphorylation level remaining unchanged upon TGF-beta 1 stimulation, Similar results were obtained using HSC4 cells, which are also growth-inhibited by TGF-beta, Smads 2 and 3 interacted with Smad4 after T beta R activation in transfected COS cells, In addition, we observed T beta R-activation-dependent interaction between Smad2 and Smad3, Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta 1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter, Dominant-negative Smad3 inhibited the transcriptional synergistic response by Smad2 and Smad4, These data suggest that TGF-beta induces heteromeric complexes of Smads 2, 3 and 4, and their concomitant translocation to the nucleus, which is required for efficient TGF-beta signal transduction.
引用
收藏
页码：5353 / 5362
页数：10
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