Novel mechanism of the co-regulation of nuclear transport of SmgGDS and rac1
Novel mechanism of the co-regulation of nuclear transport of SmgGDS and rac1
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DOI：
10.1074/jbc.m211286200
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发表时间：
2003-04-04
影响因子：
4.8
通讯作者：
Williams, CL
中科院分区：
文献类型：
--
作者：
Lanning, CC;Ruiz-Velasco, R;Williams, CL
犰狳蛋白SmgGDS通过含有C末端多碱基区（PBR）的小GTP酶（如Rac 1和RhoA）促进鸟嘌呤核苷酸交换。由于PBR类似于核定位信号（NLS）序列，因此我们研究了SmgGDS与Rac 1或RhoA的核转运。我们表明，Rac 1 PBR具有显着的NLS活性时，它融合到绿色荧光蛋白（GFP）或在全长Rac 1的上下文中。相比之下，RhoA PBR在与GFP融合时或在全长RhoA的情况下具有非常差的NLS活性。Rac 1和SmgGDS的核积累通过Rac 1激活而增强，并通过Rac 1 PBR的突变而减少。相反，SmgGDS核积累通过与RhoA的相互作用而减少。我们鉴定的SmgGDS核输出信号序列促进SmgGDS核输出。这些结果表明SmgGDS-Rac 1复合物在细胞核中积累，因为Rac 1 PBR具有NLS活性，并且因为Rac 1提供适当的GTP依赖性信号。相比之下，SmgGDS（.）RhoA复合物在细胞质中积累，因为RhoA PBR不具有NLS活性。该模型可能适用于其他犰狳蛋白除了SmgGDS，因为我们证明，激活Rac 1和RhoA也提供刺激和抑制信号，分别为p120连环蛋白的核积累。这些结果表明，具有PBR的小GTP酶可以调节犰狳蛋白的核转运。
The armadillo protein SmgGDS promotes guanine nucleotide exchange by small GTPases containing a C-terminal polybasic region (PBR), such as Rac1 and RhoA. Because the PBR resembles a nuclear localization signal (NLS) sequence, we investigated the nuclear transport of SmgGDS with Rac1 or RhoA. We show that the Rac1 PBR has significant NLS activity when it is fused to green fluorescent protein (GFP) or in the context of full-length Rac1. In contrast, the RhoA PBR has very poor NLS activity when it is fused to GFP or in the context of full-length RhoA. The nuclear accumulation of both Rac1 and SmgGDS is enhanced by Rac1 activation and diminished by mutation of the Rac1 PBR. Conversely, SmgGDS nuclear accumulation is diminished by interactions with RhoA. An SmgGDS nuclear export signal sequence that we identified promotes SmgGDS nuclear export. These results suggest that SmgGDS-Rac1 complexes accumulate in the nucleus because the Rac1 PBR has NLS activity and because Rac1 supplies the appropriate GTP-dependent signal. In contrast, SmgGDS(.)RhoA complexes accumulate in the cytoplasm because the RhoA PBR does not have NLS activity. This model may be applicable to other armadillo proteins in addition to SmgGDS, because we demonstrate that activated Rac1 and RhoA also provide stimulatory and inhibitory signals, respectively, for the nuclear accumulation of p120 catenin. These results indicate that small GTPases with a PBR can regulate the nuclear transport of armadillo proteins.