Microtubule binding to Smads may regulate TGF beta activity.


Journal Article

Smad proteins are intracellular signaling effectors 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.

Full Text

Cited Authors

  • Dong, C; Li, Z; Alvarez, R; Feng, XH; Goldschmidt-Clermont, PJ

Published Date

  • January 2000

Published In

Volume / Issue

  • 5 / 1

Start / End Page

  • 27 - 34

PubMed ID

  • 10678166

Pubmed Central ID

  • 10678166

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/s1097-2765(00)80400-1


  • eng