title: Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors.
abstract: STAT transcription factors are tyrosine phosphorylated upon cytokine stimulation and enter the nucleus to activate target genes. We show that Rac1 and a GTPase-activating protein, MgcRacGAP, bind directly to p-STAT5A and are required to promote its nuclear translocation. Using permeabilized cells, we find that nuclear translocation of purified p-STAT5A is dependent on the addition of GTP-bound Rac1, MgcRacGAP, importin alpha, and importin beta. p-STAT3 also enters the nucleus via this transport machinery, and mutant STATs lacking the MgcRacGAP binding site do not enter the nucleus even after phosphorylation. We conclude that GTP-bound Rac1 and MgcRacGAP function as a nuclear transport chaperone for activated STATs.
authors.affiliation: Division of Cellular Therapy, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kawashima
authors.forename: Ying Chun
authors.initials: YC
authors.lastname: Bao
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nomura
authors.forename: Yuseok
authors.initials: Y
authors.lastname: Moon
authors.forename: Yukio
authors.initials: Y
authors.lastname: Tonozuka
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Minoshima
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hatori
authors.forename: Akiho
authors.initials: A
authors.lastname: Tsuchiya
authors.forename: Mari
authors.initials: M
authors.lastname: Kiyono
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nosaka
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D010766:Phosphorylation; D021381:Protein Transport; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D028901:alpha Karyopherins / Q000378:metabolism; D028961:beta Karyopherins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D050799:STAT5 Transcription Factor; D028901:alpha Karyopherins; D028961:beta Karyopherins; C115995:mgcRacGAP; D014443:Tyrosine; D020830:rac1 GTP-Binding Protein