GTP-dependent segregation of H-ras from lipid rafts is required for biological activity
GTP-dependent segregation of H-ras from lipid rafts is required for biological activity
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DOI：
10.1038/35070050
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发表时间：
2001-04-01
影响因子：
21.3
通讯作者：
Hancock, JF
中科院分区：
文献类型：
--
作者：
Prior, IA;Harding, A;Hancock, JF
不同的质膜附着位点可能是Ras亚型之间功能差异的基础。在这里，我们表明，棕榈酰化和法尼基化的目标H-ras的脂筏和小窝，但H-ras与这些膜子域的相互作用是动态的。GTP负载重新分配H-ras从筏到散装质膜的机制，需要相邻的H-ras的高变区。从筏释放H-ras-GTP是Raf有效激活所必需的。相比之下，K-ras位于筏外，与结合的核苷酸无关。我们的研究确定了一种新的蛋白质决定簇，这是所需的H-ras功能，并表明，GTP/GDP状态的H-ras决定其在质膜上的横向分离。
Different sites of plasma membrane attachment may underlie functional differences between isoforms of Ras. Here we show that palmitoylation and farnesylation targets H-ras to lipid rafts and caveolae, but that the interaction of H-ras with these membrane subdomains is dynamic. GTP-loading redistributes H-ras from rafts into bulk plasma membrane by a mechanism that requires the adjacent hypervariable region of H-ras. Release of H-ras-GTP from rafts is necessary for efficient activation of Raf. By contrast, K-ras is located outside rafts irrespective of bound nucleotide. Our studies identify a novel protein determinant that is required for H-ras function, and show that the GTP/GDP state of H-ras determines its lateral segregation on the plasma membrane.