Cao H James, Lin Hung-Yun, Luidens Mary K, Davis Faith B, Davis Paul J
Ordway Research Institute, Inc., Albany, New York 12208, USA.
Endocr Res. 2009;34(1-2):31-42. doi: 10.1080/07435800902911810.
In CV-1 cells, shuttling from cytoplasm to nucleus of the nuclear thyroid hormone receptor-beta1 (TRbeta1, TR) is shown in this report to be regulated by extracellular thyroid hormone at a hormone receptor on cell surface integrin alphav3.
The receptor was introduced into cells as a GFP-TR1 chimera and intracellular movement of the receptor was monitored by confocal microscopy of cells treated with L-thyroxine (T(4)).
TR-GFP translocation in the presence of T(4) requires activation of extracellular-regulated protein kinases 1/2 (ERK1/2). Inhibition of T(4)-binding to alphavbeta3 with anti-alphavbeta3 or Arg-Gly-Asp (RGD) peptide blocks T(4)-stimulated GFP-TR nuclear translocation, as do the hormone-binding inhibitor tetraiodothyroacetic acid (tetrac) and the ERK1/2 inhibitor, PD98059. TR1 is an ERK1/2 substrate.
Via a nongenomic mechanism initiated at plasma membrane integrin v3, T(4)-activated ERK1/2 and TR1 move transiently in an immunoprecipitable complex to the nuclei of T(4)-treated cells.
本报告显示，在CV-1细胞中，核甲状腺激素受体β1（TRβ1，TR）从细胞质到细胞核的穿梭受细胞表面整合素αvβ3上的细胞外甲状腺激素调节。
将该受体作为绿色荧光蛋白-TR1嵌合体导入细胞，并通过共聚焦显微镜监测用L-甲状腺素（T4）处理的细胞中该受体的细胞内运动。
在T4存在的情况下，TR-绿色荧光蛋白的易位需要细胞外调节蛋白激酶1/2（ERK1/2）的激活。用抗αvβ3或精氨酸-甘氨酸-天冬氨酸（RGD）肽抑制T4与αvβ3的结合，会阻断T4刺激的绿色荧光蛋白-TR核易位，激素结合抑制剂四碘甲状腺乙酸（tetrac）和ERK1/2抑制剂PD98059也会如此。TR1是ERK1/2的底物。
通过在质膜整合素v3上启动的非基因组机制，T4激活的ERK1/2和TR1在免疫沉淀复合物中短暂移动到T4处理细胞的细胞核。
