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PMID: 9384585 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Extracellular signal-dependent nuclear import of Stat1 is mediated by nuclear pore-targeting complex formation with NPI-1, but not Rch1.

The EMBO journal ·Vol. 16 ·No. 23 ·1997-12-01 ·Pages 7067-77

Sekimoto T, Imamoto N, Nakajima K, Hirano T, Yoneda Y

Abstract

In response to interferon-gamma (IFN-gamma), Stat1 is tyrosine phosphorylated and translocates to the nucleus where it activates transcription. In this study, we identified factors which mediate the nuclear import of Stat1. Tyrosine-phosphorylated Stat1 associated with the beta subunit (a 97 kDa component) of the nuclear pore-targeting complex via the NPI-1 family, but not the Rch1 family, of alpha subunit (a 58 kDa component) as a result of IFN-gamma stimulation. Antibodies against NPI-1 or beta subunit consistently inhibited the IFN-gamma-dependent nuclear import of Stat1 in living cells, although antibodies reactive to Rch1 had no effect. Solution binding assays with deletion mutants of NPI-1 showed that the Stat1-binding domain of NPI-1 was located in the carboxy-terminal region, which is clearly distinct from the SV40 large T antigen nuclear localization signal (NLS)-binding region. These results indicate that the extracellular signal-dependent nuclear transport of Stat1 is mediated by NPI-1, but not Rch1, in conjunction with beta subunit, and that these factors participate in, not only constitutive, but also the conditional nuclear import of proteins.

MeSH Terms
Binding Sites Biological Transport Carrier Proteins/metabolism Cell Compartmentation Cytokines/pharmacology Cytoplasm/metabolism DNA-Binding Proteins/metabolism Interferon-gamma/pharmacology Nuclear Envelope/metabolism Nuclear Localization Signals Nuclear Proteins/metabolism Phosphorylation Phosphotyrosine/metabolism Protein Binding STAT1 Transcription Factor Signal Transduction Trans-Activators/metabolism alpha Karyopherins
Chemicals
Carrier Proteins Cytokines DNA-Binding Proteins Nuclear Localization Signals Nuclear Proteins STAT1 Transcription Factor Trans-Activators alpha Karyopherins karyopherin alpha 2 Phosphotyrosine Interferon-gamma
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sekimoto T
Department of Anatomy and Cell Biology, Biomedical Research Center, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565, Japan.
Imamoto N
Nakajima K
Hirano T
Yoneda Y
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/16.23.7067
Published
1997-12-01
Pages
7067-77
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170309
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/16.23.7067 PMC Full Text View journal details
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