Association of mouse actin-binding protein 1 (mAbp1/SH3P7), an Src kinase target, with dynamic regions of the cortical actin cytoskeleton in response to Rac1 activation

Association of mouse actin-binding protein 1 (mAbp1/SH3P7), an Src kinase target, with dynamic regions of the cortical actin cytoskeleton in response to Rac1 activation
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DOI:
10.1091/mbc.11.1.393
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发表时间:
2000-01-01
影响因子:
3.3
通讯作者:
Drubin, DG
Drubin, DG
中科院分区:
生物学3区
文献类型:
--
作者:
Kessels, MM;Engqvist-Goldstein, ÅEY;Drubin, DG

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酵母Abp 1 p是一种皮质肌动蛋白细胞骨架蛋白,参与细胞骨架调节、内吞作用和cAMP信号传导。我们已经确定了一个基因编码的小鼠同源的Abp 1 p,它是相同的SH 3 P7,最近被证明是Src酪氨酸激酶的目标蛋白。酵母和小鼠Abp 1 p显示相同的结构域结构,包括N-末端肌动蛋白解聚因子同源结构域和C-末端Src同源3结构域。使用两个独立的肌动蛋白结合结构域,mAbp 1结合肌动蛋白丝与1:5的饱和化学计量。在静止细胞中,mAbp 1与皮质F-肌动蛋白共定位在代表细胞生长位点的成纤维细胞突起中。mAbp 1出现在迁移细胞的肌动蛋白丰富的前沿。生长因子导致mAbp 1在板状伪足中迅速积累。这种反应可以通过显性阳性Rad的表达来模拟。mAbp 1的募集似乎依赖于肌动蛋白的重新聚合,并且特异性地发生在Arp 2/3复合物富集的位点。mAbp 1是一种新发现的小鼠细胞骨架蛋白,可能作为动态皮质肌动蛋白细胞骨架和膜动力学区域之间的信号响应链接。
Yeast Abp1p is a cortical actin cytoskeleton protein implicated in cytoskeletal regulation, endocytosis, and cAMP-signaling. We have identified a gene encoding a mouse homologue of Abp1p, and it is identical to SH3P7, a protein shown recently to be a target of Src tyrosine kinases. Yeast and mouse Abp1p display the same domain structure including an N-terminal actin-depolymerizing factor homology domain and a C-terminal Src homology 3 domain. Using two independent actin-binding domains, mAbp1 binds to actin filaments with a 1:5 saturation stoichiometry. In stationary cells, mAbp1 colocalizes with cortical F-actin in fibroblast protrusions that represent sites of cellular growth. mAbp1 appears at the actin-rich leading edge of migrating cells. Growth factors cause mAbp1 to rapidly accumulate in lamellipodia. This response can be mimicked by expression of dominant-positive Rad. mAbp1 recruitment appears to be dependent on de novo actin polymerization and occurs specifically at sites enriched for the Arp2/3 complex. mAbp1 is a newly identified cytoskeletal protein in mice and may serve as a signal-responsive link between the dynamic cortical actin cytoskeleton and regions of membrane dynamics.