Multiple Rho proteins regulate the subcellular targeting of PAK5
Multiple Rho proteins regulate the subcellular targeting of PAK5
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DOI：
10.1016/j.bbrc.2006.09.172
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发表时间：
2006-12-15
影响因子：
3.1
通讯作者：
Frost, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Wu, Xiaochong;Frost, Jeffrey A.
我们研究了控制 p21 激活激酶 5 (PAK5) 亚细胞定位的调控机制，发现 PAK5 内的 Cdc42/Rac 相互作用结合 (CRIB) 结构域对于细胞内的正确靶向至关重要。我们还观察到，除了 Cdc42 之外，PAK5 还与 RhoD 和 RhoH 相互作用，并且与 RhoD 的相互作用将 PAK5 靶向与 Cdc42 刺激的亚细胞位置不同的亚细胞位置。通过缺失分析，我们观察到 PAK5 的线粒体定位是由多个结构域控制的，这提供了 PAK5 的激酶活性对其在线粒体上循环和脱离线粒体的能力至关重要的证据，并证明激酶失活的 PAK5 的表达会对线粒体形态产生显着影响。这些数据表明，PAK5 通过不同的 Rho 家族小 G 蛋白以及内在靶向序列定向至不同的亚细胞位置。 (c) 2006 Elsevier Inc. 保留所有权利。
We investigated the regulatory mechanisms controlling the subcellular localization of p21-activated kinase 5 (PAK5) and found that the Cdc42/Rac interactive binding (CRIB) domain within PAK5 is critical for proper targeting within the cell. We also observed that PAK5 interacts with RhoD and RhoH in addition to Cdc42, and that interaction with RhoD targets PAK5 to subcellular locations that are distinct from those stimulated by Cdc42. Through deletion analysis we observed that the mitochondrial localization of PAK5 is controlled by multiple domains, providing evidence that the kinase activity of PAK5 is critical to its ability to cycle on and off mitochondria, and demonstrate that expression of kinase-inactive PAK5 elicits dramatic effects on mitochondrial morphology. These data indicate that PAK5 is directed to distinct subcellular locations by different Rho family small G proteins as well as by intrinsic targeting sequences. (c) 2006 Elsevier Inc. All rights reserved.