Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors

Toshiyuki Kawashima, Chun Bao Ying, Yasushi Nomura, Yuseok Moon, Yukio Tonozuka, Yukinori Minoshima, Tomonori Hatori, Akiho Tsuchiya, Mari Kiyono, Tetsuya Nosaka, Hideaki Nakajima, David A. Williams, Toshio Kitamura

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74 Citations (Scopus)

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 α, and importin β. 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.

Original languageEnglish
Pages (from-to)937-946
Number of pages10
JournalJournal of Cell Biology
Volume175
Issue number6
DOIs
Publication statusPublished - 2006 Dec 18

ASJC Scopus subject areas

  • Cell Biology

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    Kawashima, T., Ying, C. B., Nomura, Y., Moon, Y., Tonozuka, Y., Minoshima, Y., Hatori, T., Tsuchiya, A., Kiyono, M., Nosaka, T., Nakajima, H., Williams, D. A., & Kitamura, T. (2006). Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors. Journal of Cell Biology, 175(6), 937-946. https://doi.org/10.1083/jcb.200604073