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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.

SUBMITTER: Kawashima T

PROVIDER: S-EPMC2064703 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature

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

Kawashima Toshiyuki T 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

The Journal of cell biology 20061201 6

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 ...[more]

PMID: 17178910

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