Conversion of mechanical force into biochemical signaling
Conversion of mechanical force into biochemical signaling
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DOI：
10.1074/jbc.m406880200
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发表时间：
2004-12-24
影响因子：
4.8
通讯作者：
Liu, MY
中科院分区：
文献类型：
--
作者：
Han, B;Bai, XH;Liu, MY
物理力通过激活细胞内信号转导通路在调节细胞增殖、分化和死亡中起重要作用。然而，细胞如何感知机械刺激在很大程度上是未知的。大多数研究集中在细胞膜蛋白，如离子通道，整合素和生长因子受体作为机械感觉单位。在这里，我们表明，机械拉伸诱导的c-Src蛋白酪氨酸激酶激活介导的肌动蛋白抑制相关蛋白（AFAP）。AFAP沿着肌动蛋白丝分布，通过与c-Src同源3和/或2结构域结合直接激活c-Src。AFAP上这些特异性结合位点的突变阻断了机械拉伸诱导的c-Src激活。因此，机械力可以沿着细胞骨架传递，细胞骨架相关蛋白和与信号转导相关的酶之间的相互作用可以将物理力转化为生化反应。细胞骨架变形诱导的蛋白质-蛋白质相互作用通过特异性结合位点可能代表细胞感受机械刺激的一种新的细胞内机制。
Physical forces play important roles in regulating cell proliferation, differentiation, and death by activating intracellular signal transduction pathways. How cells sense mechanical stimulation, however, is largely unknown. Most studies focus on cellular membrane proteins such as ion channels, integrins, and receptors for growth factors as mechanosensory units. Here we show that mechanical stretch-induced c-Src protein tyrosine kinase activation is mediated through the actin filament-associated protein ( AFAP). Distributed along the actin filaments, AFAP can directly active c-Src through binding to its Src homology 3 and/or 2 domains. Mutations at these specific binding sites on AFAP blocked mechanical stretch-induced c-Src activation. Therefore, mechanical force can be transmitted along the cytoskeleton, and interaction between cytoskeletal associated proteins and enzymes related to signal transduction may convert physical forces into biochemical reactions. Cytoskeleton deformation-induced protein-protein interaction via specific binding sites may represent a novel intracellular mechanism for cells to sense mechanical stimulation.