A Rac1 effector site controlling mitogenesis through superoxide production
A Rac1 effector site controlling mitogenesis through superoxide production
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DOI：
10.1074/jbc.273.29.17991
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发表时间：
1998-07-17
影响因子：
4.8
通讯作者：
Bar-Sagi, D
中科院分区：
文献类型：
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作者：
Joneson, T;Bar-Sagi, D
Rac GTP结合蛋白控制对有丝分裂和肿瘤发生至关重要的信号转导途径（1，2）。这些信号通路的生物化学性质目前尚不清楚。在这里，我们报告的区域（残基124-135），以前被定义为插入区（3），是必不可少的有丝分裂活性。该区域的缺失不干扰拉德诱导细胞骨架变化或激活Jun激酶丝裂原活化蛋白激酶级联的能力，但消除了拉德诱导的DNA合成刺激和拉德介导的超氧化物产生在静止的成纤维细胞。用消除超氧化物生成的试剂处理细胞特异性地抑制Rad的促有丝分裂作用。我们的研究结果确定了一个效应器网站在拉德是必要的促有丝分裂信号和牵连超氧化物生成作为候选效应器途径Rac 1依赖细胞生长。
The Rac GTP-binding protein controls signal transduction pathways that are critical for mitogenesis and oncogenesis (1, 2). The biochemical nature of these signaling pathways is presently unknown. Here we report that a region in Rad (residues 124-135), previously defined as the insert region (3), is essential for its mitogenic activity. Deletion of this region does not interfere with the ability of Rad to induce cytoskeletal changes or to activate the Jun kinase mitogen-activated protein kinase cascade but abrogates Rad-induced stimulation of DNA synthesis and Rad-mediated superoxide production in quiescent fibroblasts. Treatment of cells with agents that abolish superoxide generation inhibits specifically the mitogenic effect of Rad. Our results identify an effector site in Rad that is necessary for mitogenic signaling and implicate superoxide generation as a candidate effector pathway of Rac1 dependent cell growth.