uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Transforming growth factor-beta induces nuclear import of Smad3 in an importin-beta1 and Ran-dependent manner
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Show others and affiliations
2001 (English)In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 12, no 4, 1079-1091 p.Article in journal (Refereed) Published
Abstract [en]

Smad proteins are cytoplasmic signaling effectors of transforming growth factor-beta (TGF-beta) family cytokines and regulate gene transcription in the nucleus. Receptor-activated Smads (R-Smads) become phosphorylated by the TGF-beta type I receptor. Rapid and precise transport of R-Smads to the nucleus is of crucial importance for signal transduction. By focusing on the R-Smad Smad3 we demonstrate that 1) only activated Smad3 efficiently enters the nucleus of permeabilized cells in an energy- and cytosol-dependent manner. 2) Smad3, via its N-terminal domain, interacts specifically with importin-beta1 and only after activation by receptor. In contrast, the unique insert of exon3 in the N-terminal domain of Smad2 prevents its association with importin-beta1. 3) Nuclear import of Smad3 in vivo requires the action of the Ran GTPase, which mediates release of Smad3 from the complex with importin-beta1. 4) Importin-beta1, Ran, and p10/NTF2 are sufficient to mediate import of activated Smad3. The data describe a pathway whereby Smad3 phosphorylation by the TGF-beta receptor leads to enhanced interaction with importin-beta1 and Ran-dependent import and release into the nucleus. The import mechanism of Smad3 shows distinct features from that of the related Smad2 and the structural basis for this difference maps to the divergent sequences of their N-terminal domains.

Place, publisher, year, edition, pages
2001. Vol. 12, no 4, 1079-1091 p.
Keyword [en]
Active Transport; Cell Nucleus, Animals, Binding Sites, Carrier Proteins/metabolism, Cell Line, Cell Line; Transformed, Cell Nucleus/*metabolism, DNA-Binding Proteins/*metabolism, Humans, Karyopherins, Mice, Nuclear Proteins/*metabolism, Nucleocytoplasmic Transport Proteins, Research Support; Non-U.S. Gov't, Signal Transduction, Trans-Activators/*metabolism, Transforming Growth Factor beta/*metabolism, Tumor Cells; Cultured, ran GTP-Binding Protein/*metabolism
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-73352DOI: 10.1091/mbc.12.4.1079PubMedID: 11294908OAI: oai:DiVA.org:uu-73352DiVA: diva2:101262
Available from: 2005-06-02 Created: 2005-06-02 Last updated: 2013-11-04Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=11294908&dopt=Citation

Authority records BETA

Heldin, Carl-HenrikMoustakas, Aristidis

Search in DiVA

By author/editor
Heldin, Carl-HenrikMoustakas, Aristidis
By organisation
Ludwig Institute for Cancer Research
In the same journal
Molecular Biology of the Cell
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 767 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf