Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors.
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.
Kawashima
Toshiyuki
T
Division of Cellular Therapy, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Bao
Ying Chun
YC
Nomura
Yasushi
Y
Moon
Yuseok
Y
Tonozuka
Yukio
Y
Minoshima
Yukinori
Y
Hatori
Tomonori
T
Tsuchiya
Akiho
A
Kiyono
Mari
M
Nosaka
Tetsuya
T
Nakajima
Hideaki
H
Williams
David A
DA
Kitamura
Toshio
T
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*
D020690:GTPase-Activating Proteins; D050799:STAT5 Transcription Factor; D028901:alpha Karyopherins; D028961:beta Karyopherins; C115995:mgcRacGAP; D014443:Tyrosine; D020830:rac1 GTP-Binding Protein