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

doi:10.1083/jcb.200604073

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

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

75 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 language	English
Pages (from-to)	937-946
Number of pages	10
Journal	Journal of Cell Biology
Volume	175
Issue number	6
DOIs	https://doi.org/10.1083/jcb.200604073
Publication status	Published - 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

Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors. / Kawashima, Toshiyuki; Ying, Chun Bao; Nomura, Yasushi; Moon, Yuseok; Tonozuka, Yukio; Minoshima, Yukinori; Hatori, Tomonori; Tsuchiya, Akiho; Kiyono, Mari; Nosaka, Tetsuya; Nakajima, Hideaki; Williams, David A.; Kitamura, Toshio.

In: Journal of Cell Biology, Vol. 175, No. 6, 18.12.2006, p. 937-946.

Research output: Contribution to journal › Article › peer-review

Kawashima, T, Ying, CB, Nomura, Y, Moon, Y, Tonozuka, Y, Minoshima, Y, Hatori, T, Tsuchiya, A, Kiyono, M, Nosaka, T, Nakajima, H, Williams, DA & Kitamura, T 2006, 'Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors', Journal of Cell Biology, vol. 175, no. 6, pp. 937-946. https://doi.org/10.1083/jcb.200604073

Kawashima, Toshiyuki ; Ying, Chun Bao ; Nomura, Yasushi ; Moon, Yuseok ; Tonozuka, Yukio ; Minoshima, Yukinori ; Hatori, Tomonori ; Tsuchiya, Akiho ; Kiyono, Mari ; Nosaka, Tetsuya ; Nakajima, Hideaki ; Williams, David A. ; Kitamura, Toshio. / Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors. In: Journal of Cell Biology. 2006 ; Vol. 175, No. 6. pp. 937-946.

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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.",

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T1 - Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors

AU - Kawashima, Toshiyuki

AU - Ying, Chun Bao

AU - Nomura, Yasushi

AU - Moon, Yuseok

AU - Tonozuka, Yukio

AU - Minoshima, Yukinori

AU - Hatori, Tomonori

AU - Tsuchiya, Akiho

AU - Kiyono, Mari

AU - Nosaka, Tetsuya

AU - Nakajima, Hideaki

AU - Williams, David A.

AU - Kitamura, Toshio

PY - 2006/12/18

Y1 - 2006/12/18

N2 - 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.

AB - 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.

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