Signal Regulation

Microtubules Regulate Signaling

Science's STKE  08 Feb 2000:
Vol. 2000, Issue 18, pp. tw2
DOI: 10.1126/stke.2000.18.tw2

Signaling by transforming growth factor-β(TGF-β) through the TGF-β2/ TGF-β1 receptor heteroligomer leads to phosphorylation of Smad proteins 2 and 3, which then bind to Smad4 and are translocated to the nucleus and regulate transcription. Dong et al. demonstrated that endogenous Smad2, 3, and 4 colocalize and coimmunoprecipitate with microtubules. Further characterization of the Smad2 interaction showed that TGF-β caused dissociation of Smad2 from microtubules. Drugs that disrupt microtubules caused release of Smad2 from microtubules, increased phosphorylation of Smad2, and increased activation of reporter genes with TGF-β-responsive promoters in both TGF-β-treated and untreated cells. Microtubules may serve as negative regulators of TGF-β signaling by controlling the availability of Smad proteins for interaction with the TGF-β receptor.

Dong, C., Li, Z., Alvarez Jr., R., Feng, X.-H., Goldschmidt-Clermont, P.J. (2000) Microtubule binding to Smads may regulate TGFβ activity. Mol. Cell 5: 27-34. [Online Journal]