Signal-regulated activation of serum response factor is mediated by changes in actin dynamics
Signal-regulated activation of serum response factor is mediated by changes in actin dynamics
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DOI：
10.1016/s0092-8674(00)81011-9
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发表时间：
1999-07-23
期刊：
影响因子：
64.5
通讯作者：
Treisman, R
中科院分区：
文献类型：
--
作者：
Sotiropoulos, A;Gineitis, D;Treisman, R
血清反应因子（SRF）调节许多血清诱导和肌肉特异性基因的转录。使用功能筛选，我们确定LIM激酶-I为SRF的有效激活剂。我们表明，SRF激活LIM激酶-1是依赖于它的能力，以调节肌动蛋白酶铣削。LIM激酶活性不是血清激活SRF所必需的，但信号依赖于肌动蛋白动力学的改变。肌动蛋白结合药物、肌动蛋白特异性C2毒素和肌动蛋白过表达的研究表明，G-肌动蛋白水平控制SRF。调节肌动蛋白动力学是必要的血清诱导的一个子集的SRF靶基因，包括黏着斑蛋白，细胞骨架肌动蛋白，和SRF本身，也足以为他们的激活。肌动蛋白微铣削为血清和LIM激酶-1诱导的SRF信号传导提供了一个汇聚点。
Serum response factor (SRF) regulates transcription of many serum-inducible and muscle-specific genes. Using a functional screen, we identified LIM kinase-l as a potent activator of SRF. We show that SRF activation by LIM kinase-l is dependent on its ability to regulate actin treadmilling. LIM kinase activity is not essential for SRF activation by serum, but signals depend on alterations in actin dynamics. Studies with actin-binding drugs, the actin-specific C2 toxin, and actin overexpression demonstrate that G-actin level controls SRF. Regulation of actin dynamics is necessary for serum induction of a subset of SRF target genes, including vinculin, cytoskeletal actin, and srf itself, and also suffices for their activation. Actin treadmilling provides a convergence point for both serum- and LIM kinase-1-induced signaling to SRF.