Microtubule binding to Smads may regulate TGFβ activity
Microtubule binding to Smads may regulate TGFβ activity
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DOI：
10.1016/s1097-2765(00)80400-1
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发表时间：
2000-01-01
期刊：
影响因子：
16
通讯作者：
Goldschmidt-Clermont, PJ
中科院分区：
文献类型：
--
作者：
Dong, CM;Li, ZR;Goldschmidt-Clermont, PJ
Smad蛋白是TGF β超家族的细胞内信号传导效应物。我们发现，内源性Smad2，3和4结合微管（MT）在几个细胞系。Smads与MT的结合不需要TGF β刺激。TGF β触发从MT解离、磷酸化和Smad2和3的核转位，随后激活CCL 64细胞中的转录。通过诺考达唑、秋水仙碱或微管蛋白突变体使MT网络失稳破坏Smads和MT之间的复合物，并增加TGF β诱导的CCL 64细胞中Smad2磷酸化和转录反应。这些数据表明，MT可以作为Smads的细胞质隔离网络，控制Smad2与活化的TGF β受体I的结合和磷酸化，并提出了MT网络负调节TGF β功能的新机制。
Smad proteins are intracellular signaling effecters of the TGF beta superfamily. We show that endogenous Smad2, 3, and 4 bind microtubules (MTs) in several cell lines. Binding of Smads to MTs does not require TGF beta stimulation. TGF beta triggers dissociation from MTs, phosphorylation, and nuclear translocation of Smad2 and 3, with consequent activation of transcription in CCL64 cells. Destabilization of the MT network by nocodazole, colchicine, or a tubulin mutant disrupts the complex between Smads and MTs and increases TGF beta-induced Smad2 phosphorylation and transcriptional response in CCL64 cells. These data demonstrate that MTs may serve as a cytoplasmic sequestering network for Smads, controlling Smad2 association with and phosphorylation by activated TGF beta receptor I, and suggest a novel mechanism for the MT network to negatively regulate TGF beta function.