Microtubule binding to Smads may regulate TGFβ activity

Chunming Dong, Zhiru Li, Rene Alvarez, Xin Hua Feng, Pascal Goldschmidt-Clermont

Research output: Contribution to journalArticle

230 Citations (Scopus)

Abstract

Smad proteins are intracellular signaling effectors of the TGFβ superfamily. We show that endogenous Smad2, 3, and 4 bind microtubules (MTs) in several cell lines. Binding of Smads to MTs does not require TGFβ stimulation. TGFβ 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 TGFβ-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 TGFβ receptor I, and suggest a novel mechanism for the MT network to negatively regulate TGFβ function.

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalMolecular Cell
Volume5
Issue number1
StatePublished - Jan 1 2000
Externally publishedYes

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Microtubules
Phosphorylation
Smad Proteins
Nocodazole
Colchicine
Tubulin
Transcriptional Activation
Cell Line

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Dong, C., Li, Z., Alvarez, R., Feng, X. H., & Goldschmidt-Clermont, P. (2000). Microtubule binding to Smads may regulate TGFβ activity. Molecular Cell, 5(1), 27-34.

Microtubule binding to Smads may regulate TGFβ activity. / Dong, Chunming; Li, Zhiru; Alvarez, Rene; Feng, Xin Hua; Goldschmidt-Clermont, Pascal.

In: Molecular Cell, Vol. 5, No. 1, 01.01.2000, p. 27-34.

Research output: Contribution to journalArticle

Dong, C, Li, Z, Alvarez, R, Feng, XH & Goldschmidt-Clermont, P 2000, 'Microtubule binding to Smads may regulate TGFβ activity', Molecular Cell, vol. 5, no. 1, pp. 27-34.
Dong C, Li Z, Alvarez R, Feng XH, Goldschmidt-Clermont P. Microtubule binding to Smads may regulate TGFβ activity. Molecular Cell. 2000 Jan 1;5(1):27-34.
Dong, Chunming ; Li, Zhiru ; Alvarez, Rene ; Feng, Xin Hua ; Goldschmidt-Clermont, Pascal. / Microtubule binding to Smads may regulate TGFβ activity. In: Molecular Cell. 2000 ; Vol. 5, No. 1. pp. 27-34.
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