Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors.
Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear translocation of STAT transcription factors.
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DOI：
10.1083/jcb.200604073
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发表时间：
2006-12-18
影响因子：
7.8
通讯作者：
Kitamura, Toshio
中科院分区：
文献类型：
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作者：
Kawashima, Toshiyuki;Bao, Ying Chun;Nomura, Yasushi;Moon, Yuseok;Tonozuka, Yukio;Minoshima, Yukinori;Hatori, Tomonori;Tsuchiya, Akiho;Kiyono, Mari;Nosaka, Tetsuya;Nakajima, Hideaki;Williams, David A;Kitamura, Toshio
STAT转录因子在细胞因子刺激后被酪氨酸磷酸化并进入细胞核以激活靶基因。我们发现Rac 1和GTP酶激活蛋白MgcRacGAP直接与p-STAT 5A结合，并需要促进其核转位。使用透化细胞，我们发现纯化的p-STAT 5A的核转位依赖于GTP结合的Rac 1、MgcRacGAP、importin α和importin β的加入。p-STAT 3也通过这种转运机制进入细胞核，缺乏MgcRacGAP结合位点的突变型STAT即使在磷酸化后也不进入细胞核。我们的结论是，GTP结合的Rac 1和MgcRacGAP功能作为一个核转运伴侣激活STAT。
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.