Dephosphorylation of cofilin is regulated through Ras and requires the combined activities of the Ras-effectors MEK and PI3K
Dephosphorylation of cofilin is regulated through Ras and requires the combined activities of the Ras-effectors MEK and PI3K
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DOI：
10.1016/s0898-6568(03)00133-5
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发表时间：
2004-02-01
影响因子：
4.8
通讯作者：
Samstag, Y
中科院分区：
文献类型：
--
作者：
Nebl, G;Fischer, S;Samstag, Y
肌动蛋白细胞骨架的重塑对于多种细胞功能至关重要，包括细胞运动、细胞内运输以及信号转导和基因表达过程。 Cofilin 已被确定为肌动蛋白重组的关键介质。其活性通过 Ser-3 的可逆磷酸化进行调节。在多种细胞类型中，通过特定表面受体的刺激快速诱导丝切蛋白的去磷酸化/激活。然而，迄今为止，将受体刺激与丝切蛋白激活联系起来的信号转导级联尚未确定。在这里，我们证明 GTPase Ras 作为 cofilin 去磷酸化途径的中央调节器。因此，通过血小板源性生长因子 (PDGF) 刺激 Ras 或激活 Ras 蛋白的瞬时表达会诱导丝切蛋白的去磷酸化。重要的是，诱导肌动蛋白丝切蛋白去磷酸化需要两条 Ras 启动的信号通路的合作：Ras-Raf-MAPkinase/Erk-kinase (MEK) 和 Ras-phosphatidylinositol-3-kinase (PI3K) 效应级联。 (C) 2003 Elsevier Inc. 保留所有权利。
Remodeling of the actin cytoskeleton is crucial for a multitude of cellular functions including cell movement, intracellular transport as well as signal transduction and gene expression processes. Cofilin has been identified as a key mediator of actin reorganization. Its activity is regulated via reversible phosphorylation of ser-3. In a variety of cell types stimulation through particular surface receptors fastly induces the dephosphorylation/activation of cofilin. Yet, the signal transduction cascades linking receptor stimulation with cofilin activation have not been identified so far. Here we show that the GTPase Ras acts as a central regulator of the cofilin dephosphorylation pathway. Thus, stimulation of Ras through platelet-derived growth factor (PDGF) or transient expression of activated Ras-proteins induces the dephosphorylation of cofilin. Importantly, the cooperation of two Ras-initiated signaling pathways is required to induce cofilin dephosphorylation: a Ras-Raf-MAPkinase/Erk-kinase (MEK)- and a Ras-phosphatidylinositol-3-kinase (PI3K)-effector cascade. (C) 2003 Elsevier Inc. All rights reserved.