Katsumi Akira, Naoe Tomoki, Matsushita Tadashi, Kaibuchi Kozo, Schwartz Martin Alexander
Cardiovascular Research Center, Departments of Microbiology and Biomedical Engineering, Mellon Prostate Research Institute, University of Virginia, Charlottesville, Virginia 22908, USA.
J Biol Chem. 2005 Apr 29;280(17):16546-9. doi: 10.1074/jbc.C400455200. Epub 2005 Mar 10.
Mechanical tension is a critical determinant of cell growth, differentiation, apoptosis, migration, and development. Integrins have been implicated in sensing force but little is known about how forces are transduced to biochemical signals. We now show that mechanical strain stimulates conformational activation of integrin alphavbeta3 in NIH3T3 cells. Integrin activation is mediated by phosphoinositol 3-kinase and is followed by an increase in integrin binding to extracellular matrix proteins. Mechanical stretch stimulation of JNK was dependent on new integrin binding to extracellular matrix. These data define a molecular mechanism for the role of integrins in mechanotransduction.
机械张力是细胞生长、分化、凋亡、迁移和发育的关键决定因素。整合素被认为与力感知有关，但对于力如何转化为生化信号却知之甚少。我们现在表明，机械应变可刺激NIH3T3细胞中整合素αvβ3的构象活化。整合素活化由磷酸肌醇3激酶介导，随后整合素与细胞外基质蛋白的结合增加。JNK的机械拉伸刺激依赖于整合素与细胞外基质的新结合。这些数据定义了整合素在机械转导中作用的分子机制。
