Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils

Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils
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DOI:
10.1038/ni1081
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发表时间:
2004-07-01
期刊:
影响因子:
30.5
通讯作者:
Williams, DA
Williams, DA
中科院分区:
医学1区
文献类型:
--
作者:
Filippi, MD;Harris, CE;Williams, DA

文献摘要

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尽管具有高度的序列相似性,Rho 鸟苷三磷酸酶 Rac1 和 Rac2 调节中性粒细胞中的不同功能。在这里,我们证明了中性粒细胞中独特的 Rac2 定位和功能是由两个独立的 C 末端基序(高变结构域和天冬氨酸 150)调节的,其中一个基序之前尚未与 Rho GTPases 的功能联系起来。此外,我们在这些相同的细胞中显示出 Rac1 定位对 Rac2 活性的意外依赖性,证明了两种密切相关的 Rho GTPases 之间存在一定程度的串扰。因此,我们在 Rac 中定义了特定序列,用于指定亚细胞定位并确定 Rac2 在中性粒细胞趋化性和超氧化物生成中的特异性。
Despite having a high degree of sequence similarity, the Rho guanosine triphosphatases Rac1 and Rac2 regulate distinct functions in neutrophils. Here we demonstrate that the unique Rac2 localization and functions in neutrophils are regulated by two separate C-terminal motifs, the hypervariable domain and aspartic acid 150, one of which has not previously been linked to the function of Rho GTPases. In addition, we show an unexpected dependence of Rac1 localization on Rac2 activity in these same cells, demonstrating a degree of crosstalk between two closely related Rho GTPases. Thus, we have defined specific sequences in Rac that specify subcellular localization and determine the specificity of Rac2 in neutrophil chemotaxis and superoxide generation.