Goldmann Wolfgang H
Center for Medical Physics and Technology, Biophysics Group, Friedrich-Alexander-University of Erlangen-Nuremberg, Henkestrasse 91, 91052, Erlangen, Germany.
Cell Biol Int. 2014 Mar;38(3):283-6. doi: 10.1002/cbin.10204. Epub 2013 Nov 27.
Adherent cells, when mechanically stressed, show a wide range of responses including large-scale changes in their mechanical behaviour and gene expression pattern. This is in part facilitated by activating the focal adhesion (FA) protein p130Cas through force-induced conformational changes that lead to the phosphorylation by src family kinases. Janostiak et al. [Janostiak et al. Cell Mol Life Sci (2013) DOI 10.1007/s00018-013-1450-x] have reported that the phosphorylation site Y12 on the SH3 domain of p130Cas modulates the binding with vinculin, a prominent mechano-coupling protein in FAs. Tension changes in FAs (due to the anchorage of the SH3 domain and C-terminal) bring about an extension of the substrate domain of p130Cas by unmasking the phosphorylation sites. These observations demonstrate that vinculin is an important modulator of the p130Cas-mediated mechano-transduction pathway in cells. The central aim should be now to test that vinculin is critical for p130Cas incorporation into the focal adhesion complex and for transmitting forces to the p130Cas molecule.
贴壁细胞在受到机械应力时，会表现出广泛的反应，包括其力学行为和基因表达模式的大规模变化。这部分是通过力诱导的构象变化激活粘着斑（FA）蛋白p130Cas来实现的，这种变化会导致src家族激酶的磷酸化。Janostiak等人[Janostiak等人，《细胞与分子生命科学》（2013年），DOI 10.1007/s00018-013-1450-x]报道，p130Cas的SH3结构域上的磷酸化位点Y12调节与纽蛋白的结合，纽蛋白是粘着斑中一种重要的机械偶联蛋白。粘着斑中的张力变化（由于SH3结构域和C末端的锚定）通过暴露磷酸化位点导致p130Cas的底物结构域延伸。这些观察结果表明，纽蛋白是细胞中p130Cas介导的机械转导途径的重要调节因子。现在的核心目标应该是测试纽蛋白对于p130Cas整合到粘着斑复合物中以及将力传递到p130Cas分子是否至关重要。
