Department of Biochemistry, Gyeongsang National University, School of Medicine, Jinju, South Korea.
Biochem Biophys Res Commun. 2010 Nov 26;402(4):736-41. doi: 10.1016/j.bbrc.2010.10.097. Epub 2010 Oct 25.
Caveolin-1, a main structural protein constituent of caveolae, plays an important role in the signal transduction, endocytosis, and cholesterol transport. In addition, caveolin-1 has conflictive role in the regulation of cell survival and death depending on intracellular signaling pathways. The receptor tyrosine kinase TrkA has been known to interact with caveolin-1, and exploits multiple functions such as cell survival, death and differentiation. In this report, we investigated how TrkA-induced cell death signaling is regulated by caveolin-1 in both TrkA and caveolin-1 overexpressing stable U2OS cells. Here we show that TrkA co-localizes with caveolin-1 mostly as a large aggresome around nucleus by confocal immunofluorescence microscopy. Interestingly, TrkA-mediated Bak cleavage was suppressed by caveolin-1, indicating an inhibition of TrkA-induced cell death signaling by caveolin-1. Moreover, caveolin-1 altered TrkA modification including tyrosine-490 phosphorylation and unidentified cleavage(s), resulting in the inhibition of TrkA-induced apoptotic cell death. Our results suggest that caveolin-1 could suppress TrkA-mediated pleiotypic effects by altering TrkA modification via functional interaction.
窖蛋白-1 是质膜窖的主要结构蛋白成分，在信号转导、内吞作用和胆固醇转运中发挥重要作用。此外，窖蛋白-1 在细胞存活和死亡的调节中具有矛盾的作用，这取决于细胞内的信号通路。原肌球蛋白受体激酶 TrkA 已被证实与窖蛋白-1 相互作用，并发挥多种功能，如细胞存活、死亡和分化。在本报告中，我们研究了在 TrkA 和窖蛋白-1 过表达稳定 U2OS 细胞中，窖蛋白-1 如何调节 TrkA 诱导的细胞死亡信号。我们发现，通过共聚焦免疫荧光显微镜观察，TrkA 与窖蛋白-1 主要在核周围作为大的聚集物共定位。有趣的是，窖蛋白-1 抑制了 TrkA 介导的 Bak 切割，表明窖蛋白-1 抑制了 TrkA 诱导的细胞死亡信号。此外，窖蛋白-1 改变了 TrkA 的修饰，包括酪氨酸-490 磷酸化和未识别的切割，从而抑制了 TrkA 诱导的凋亡性细胞死亡。我们的结果表明，窖蛋白-1 可以通过与 TrkA 的功能相互作用改变 TrkA 的修饰来抑制 TrkA 介导的多效性效应。
