PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia

PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia
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DOI:
10.1093/emboj/17.22.6527
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发表时间:
1998-11-16
期刊:
影响因子:
11.4
通讯作者:
Minden, A
Minden, A
中科院分区:
生物学1区
文献类型:
--
作者:
Abo, A;Qu, J;Minden, A

文献摘要

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GTP酶Rac和Cdc42Hs控制多种细胞功能。除了作为细胞内信号级联的介质,它们在细胞形态发生和有丝分裂中具有重要作用。我们已经确定了一种新的PAK相关的激酶,PAK4,作为一个新的效应分子Cdc42Hs。PAK4仅通过其GTP酶结合结构域(GBD)与活化形式的Gdc42H相互作用。PAK4和组成型活性Cdc42HsV12的GO表达导致PAK4重新分布到高尔基体膜的布雷菲德菌素A敏感区室,并随后诱导丝状伪足和肌动蛋白聚合。重要的是,肌动蛋白细胞骨架的重组依赖于PAK4激酶活性及其与Cdc42Hs的相互作用。因此,与PAK家族的其他成员不同,PAK4在Cdc42Hs和肌动蛋白细胞骨架之间提供了一种新的联系。PAK4和Cdc42Hs的细胞位置表明高尔基体在细胞形态发生中的作用。
The GTPases Rac and Cdc42Hs control diverse cellular functions. In addition to being mediators of intracellular signaling cascades, they have important roles in cell morphogenesis and mitogenesis. We have identified a novel PAK-related kinase, PAK4, as a new effector molecule for Cdc42Hs. PAK4 interacts only with the activated form of Gdc42Hs through its GTPase-binding domain (GBD). Go-expression of PAK4 and the constitutively active Cdc42HsV12 causes the redistribution of PAK4 to the brefeldin A-sensitive compartment of the Golgi membrane and the subsequent induction of filopodia and actin polymerization. Importantly, the reorganization of the actin cytoskeleton is dependent on PAK4 kinase activity and on its interaction with Cdc42Hs. Thus, unlike other members of the PAK family, PAK4 provides a novel link between Cdc42Hs and the actin cytoskeleton. The cellular locations of PAK4 and Cdc42Hs suggest a role for the Golgi in cell morphogenesis.