Filamin Associates with Smads and Regulates Transforming Growth Factor-β Signaling

Aya Sasaki, Yoshiko Masuda, Yasutaka Ohta, Kyoji Ikeda, Ken Watanabe

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Members of the Smad proteins transmit signals triggered by the ligands of transforming growth factor (TGF)-β 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-β/activin receptor-regulated Smad2. TGF-β signaling was defective in filamin-deficient human melanoma cells M2 compared with a filamin-transfected subline A7, as determined by TGF-β-responsive reporter gene activation and Smad2 nuclear accumulation. M2 cells restored TGF-β responsiveness following transient transfection of full-length filamin encoding vector. The defective TGF-β signaling in M2 cells seemed to be due to impaired receptor-induced serine phosphorylation of Smad2. These results suggest that filamin plays an important role in Smad-mediated signaling.

Original languageEnglish
Pages (from-to)17871-17877
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number21
DOIs
Publication statusPublished - 2001 Jan 25
Externally publishedYes

Fingerprint

Filamins
Transforming Growth Factors
Smad Proteins
Phosphorylation
Smad5 Protein
Genes
Activin Receptors
Ligands
Microfilament Proteins
Cytoskeletal Proteins
Growth Factor Receptors
Transcription
Reporter Genes
Yeast
Serine
Transcriptional Activation
Transfection
Melanoma
Screening
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Filamin Associates with Smads and Regulates Transforming Growth Factor-β Signaling. / Sasaki, Aya; Masuda, Yoshiko; Ohta, Yasutaka; Ikeda, Kyoji; Watanabe, Ken.

In: Journal of Biological Chemistry, Vol. 276, No. 21, 25.01.2001, p. 17871-17877.

Research output: Contribution to journalArticle

Sasaki, Aya ; Masuda, Yoshiko ; Ohta, Yasutaka ; Ikeda, Kyoji ; Watanabe, Ken. / Filamin Associates with Smads and Regulates Transforming Growth Factor-β Signaling. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 21. pp. 17871-17877.
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