The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338
The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338
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DOI：
10.1038/24184
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发表时间：
1998-11-12
期刊：
影响因子：
64.8
通讯作者：
Marshall, MS
中科院分区：
文献类型：
--
作者：
King, AJ;Sun, HY;Marshall, MS
涉及信号传导的途径：蛋白质p21（Ras）将一系列细胞外信号从细胞膜上的受体传播到细胞质和细胞核（1）。Ras蛋白调节许多效应物，包括Raf蛋白激酶家族的成员。Raf-1在质膜上的Ras依赖性活化涉及磷酸化事件、蛋白质-蛋白质相互作用和结构变化（2-8）。Raf-1催化结构域中丝氨酸残基338或339的磷酸化调节其响应Ras、Src和表皮生长因子的活化（9，10）。在这里，我们表明，p21激活的蛋白激酶Pak 3磷酸化Raf-1的丝氨酸338在体外和体内。p21活化蛋白激酶受Rho家族GTP酶Rac和Cdc 42调节（参考文献11）。我们的研究结果表明，通过Raf-1的信号转导依赖于Ras和Pak通路的激活。由于Ras依赖性磷脂酰肌醇-3-OH激酶可刺激Rac上的鸟嘌呤核苷酸交换活性（12，13），因此可能存在一种机制，通过该机制，一种Ras效应物途径可受到另一种Ras效应物途径的影响。
The pathway involving the signalling: protein p21(Ras) propagates a range of extracellular signals from receptors on the cell membrane to the cytoplasm and nucleus(1). The Ras proteins regulate many effecters, including members of the Raf family of protein kinases. Ras-dependent activation of Raf-1 at the plasma membrane involves phosphorylation events, protein-protein interactions and structural changes(2-8). Phosphorylation of serine residues 338 or 339 in the catalytic domain of Raf-1 regulates its activation in response to Ras, Src and epidermal growth factor(9,10). Here we show that the p21-activated protein kinase Pak3 phosphorylates Raf-1 on serine 338 in vitro and in vivo. The p21-activated protein kinases are regulated by the Rho-family GTPases Rac and Cdc42 (ref, 11). Our results indicate that signal transduction through Raf-1 depends on both Ras and the activation of the Pak pathway. As guanine-nucleotide-exchange activity on Rac can be stimulated by a Ras-dependent phosphatidylinositol-3-OH kinase(12,13), a mechanism could exist through which one Ras effector pathway can be influenced by another.