title: Extracellular signal-dependent nuclear import of STAT3 is mediated by various importin alphas.
abstract: The signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is involved in a variety of biological functions. STAT3 is activated by cytokines and growth factors via the phosphorylation of a tyrosine residue, dimerization, and subsequent nuclear translocation. However, the mechanism of its nuclear translocation is unclear. A study of the cytokine-stimulated import of STAT3 into the nucleus is reported herein. An oncostatin M (OSM)-dependent nuclear import assay system was first established in living cells. Using this system, we demonstrated that the microinjection of the importin alpha5/NPI-1 mutant, an anti-importin beta antibody, and the RanQ69L mutant inhibited the nuclear import of STAT3. Second, we showed that tyrosine-phosphorylated STAT3 associates, not only with importin alpha5/NPI-1 but also with other importin alphas, as a result of OSM stimulation, as evidenced by a solution binding assay. These findings suggest that the extracellular signal-dependent nuclear transport of STAT3 is mediated by various importin alphas, importin beta, and Ran.
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, Osaka City University, Osaka 558-8585, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Ushijima
authors.forename: Naoko
authors.initials: N
authors.lastname: Sakaguchi
authors.forename: Arihiro
authors.initials: A
authors.lastname: Kano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maruyama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sekimoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
authors.forename: Kenji
authors.initials: K
authors.lastname: Ogino
authors.forename: Taro
authors.initials: T
authors.lastname: Tachibana
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005973:Glutamine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D051381:Rats; D050796:STAT3 Transcription Factor; D017384:Sequence Deletion / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C494088:Stat3 protein, rat; D015534:Trans-Activators; D028901:alpha Karyopherins; D005973:Glutamine; D019000:Phosphotyrosine; D020931:ran GTP-Binding Protein