Msk is required for nuclear import of TGF-β/BMP-activated Smads

Lan Xu, Xiaohao Yao, Xiaochu Chen, Peiyuan Lu, Biliang Zhang, Y. Tony Ip

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Nuclear translocation of Smad proteins is a critical step in signal transduction of transforming growth factor β (TGF-β) and bone morphogenetic proteins (BMPs). Using nuclear accumulation of the Drosophila Smad Mothers against Decapentaplegic (Mad) as the readout, we carried out a whole-genome RNAi screening in Drosophila cells. The screen identified mole-skin (msk) as important for the nuclear import of phosphorylated Mad. Genetic evidence in the developing eye imaginal discs also demonstrates the critical functions of msk in regulating phospho-Mad. Moreover, knockdown of importin 7 and 8 (Imp7 and 8), the mammalian orthologues of Msk, markedly impaired nuclear accumulation of Smad1 in response to BMP2 and of Smad2/3 in response to TGF-β. Biochemical studies further suggest that Smads are novel nuclear import substrates of Imp7 and 8. We have thus identified new evolutionarily conserved proteins that are important in the signal transduction of TGF-β and BMP into the nucleus.

Original languageEnglish (US)
Pages (from-to)981-994
Number of pages14
JournalJournal of Cell Biology
Volume178
Issue number6
DOIs
StatePublished - Sep 10 2007
Externally publishedYes

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Bone Morphogenetic Proteins
Cell Nucleus Active Transport
Transforming Growth Factors
Karyopherins
Nevus
Drosophila
Signal Transduction
Smad Proteins
Imaginal Discs
RNA Interference
Genome
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Xu, L., Yao, X., Chen, X., Lu, P., Zhang, B., & Ip, Y. T. (2007). Msk is required for nuclear import of TGF-β/BMP-activated Smads. Journal of Cell Biology, 178(6), 981-994. https://doi.org/10.1083/jcb.200703106

Msk is required for nuclear import of TGF-β/BMP-activated Smads. / Xu, Lan; Yao, Xiaohao; Chen, Xiaochu; Lu, Peiyuan; Zhang, Biliang; Ip, Y. Tony.

In: Journal of Cell Biology, Vol. 178, No. 6, 10.09.2007, p. 981-994.

Research output: Contribution to journalArticle

Xu, L, Yao, X, Chen, X, Lu, P, Zhang, B & Ip, YT 2007, 'Msk is required for nuclear import of TGF-β/BMP-activated Smads', Journal of Cell Biology, vol. 178, no. 6, pp. 981-994. https://doi.org/10.1083/jcb.200703106
Xu, Lan ; Yao, Xiaohao ; Chen, Xiaochu ; Lu, Peiyuan ; Zhang, Biliang ; Ip, Y. Tony. / Msk is required for nuclear import of TGF-β/BMP-activated Smads. In: Journal of Cell Biology. 2007 ; Vol. 178, No. 6. pp. 981-994.
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