Arai Akiko, Spencer Jeffrey A, Olson Eric N
Department of Molecular Biology, University of Texas, Southwestern Medical Center at Dallas, Dallas, Texas 75390-9148, USA.
J Biol Chem. 2002 Jul 5;277(27):24453-9. doi: 10.1074/jbc.M202216200. Epub 2002 Apr 30.
Changes in actin dynamics influence diverse cellular processes and couple the actin-based cytoskeleton to changes in gene transcription. Members of the Rho GTPase family regulate cytoskeletal organization by stimulating actin polymerization and stress fiber formation when activated by extracellular signaling. The transcriptional activity of serum response factor (SRF) is stimulated in response to changes in actin dynamics and Rho signaling, but the proteins that mediate this phenomenon have not been fully identified. We describe a novel, evolutionarily conserved actin-binding protein, called STARS (striated muscle activator of Rho signaling), that is expressed specifically in cardiac and skeletal muscle cells. STARS binds to the I-band of the sarcomere and to actin filaments in transfected cells, where it activates Rho-signaling events. STARS stimulates the transcriptional activity of SRF through a mechanism that requires actin binding and involves Rho GTPase activation. STARS provides a potential mechanism for specifically enhancing Rho-dependent transcription in muscle cells and for linking changes in actin dynamics to gene transcription.
肌动蛋白动力学的变化会影响多种细胞过程,并将基于肌动蛋白的细胞骨架与基因转录的变化联系起来。Rho GTPase家族成员在被细胞外信号激活时,通过刺激肌动蛋白聚合和应力纤维形成来调节细胞骨架组织。血清反应因子(SRF)的转录活性会因肌动蛋白动力学和Rho信号的变化而受到刺激,但介导这一现象的蛋白质尚未完全确定。我们描述了一种新的、进化上保守的肌动蛋白结合蛋白,称为STARS(Rho信号的横纹肌激活剂),它特异性地表达于心肌和骨骼肌细胞中。STARS与肌节的I带以及转染细胞中的肌动蛋白丝结合,在那里它激活Rho信号事件。STARS通过一种需要肌动蛋白结合并涉及Rho GTPase激活的机制来刺激SRF的转录活性。STARS为特异性增强肌肉细胞中Rho依赖性转录以及将肌动蛋白动力学变化与基因转录联系起来提供了一种潜在机制。