Filamin associates with Smads and regulates transforming growth factor-β signaling

被引:140
作者
Sasaki, A
Masuda, Y
Ohta, Y
Ikeda, K
Watanabe, K
机构
[1] Natl Inst Longev Sci, Dept Geriatr Res, Aichi 4748522, Japan
[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA
关键词
D O I
10.1074/jbc.M008422200
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
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.
引用
收藏
页码:17871 / 17877
页数:7
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