Filamin associates with Smads and regulates transforming growth factor-β signaling
Filamin associates with Smads and regulates transforming growth factor-β signaling
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DOI：
10.1074/jbc.m008422200
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发表时间：
2001-05-25
影响因子：
4.8
通讯作者：
Watanabe, K
中科院分区：
文献类型：
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作者：
Sasaki, A;Masuda, Y;Watanabe, K
Smad蛋白的成员传递由转化生长因子(TGF)- β超家族配体触发的信号，配体激活受体诱导所谓的受体调节的Smad磷酸化，然后在细胞核中积累，与Smad相互作用蛋白协同参与靶基因转录。我们进行了酵母双杂交筛选，并鉴定了丝蛋白，一种细胞骨架肌动蛋白结合蛋白280，作为smad5相互作用蛋白。研究发现，Filamin不仅与Smad5有关，还与其他Smad蛋白有关，包括tgf - β /激活素受体调节的Smad2。通过tgf - β反应性报告基因激活和Smads核积累来确定，与丝蛋白转染亚群A7相比，丝蛋白缺乏的人黑色素瘤细胞M2中tgf - β信号通路存在缺陷。短暂转染全长丝蛋白编码载体后，M2细胞恢复了tgf - β反应性。M2细胞中tgf - β信号的缺陷似乎是由于受体诱导的Smads丝氨酸磷酸化受损。这些结果表明丝蛋白在smad介导的信号传导中起重要作用。
Members of the Smad proteins transmit signals triggered by the ligands of transforming growth factor (TGF)-beta superfamily, Ligand-activated receptors induce phosphorylation of so-called receptor-regulated Smads, which then accumulate in the nucleus to participate in target gene transcription, in collaboration with Smad-interacting proteins. We performed yeast two-hybrid screening and identified filamin, a cytoskeletal actin-binding protein 280, as a Smad5-interacting protein. Filamin was found to be associated not only with Smad5 but also with other Smad proteins, including TGF-beta/ activin receptor-regulated Smad2. TGF-beta signaling was defective in filamin-deficient human melanoma cells M2 compared with a filamin-transfected subline A7, as determined by TGF-beta -responsive reporter gene activation and Smads nuclear accumulation. M2 cells restored TGF-beta responsiveness following transient transfection of full-length filamin encoding vector. The defective TGF-beta signaling in M2 cells seemed to be due to impaired receptor-induced serine phosphorylation of Smads. These results suggest that filamin plays an important role in Smad-mediated signaling.