Riedel C, Levy O, Carrasco N
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J Biol Chem. 2001 Jun 15;276(24):21458-63. doi: 10.1074/jbc.M100561200. Epub 2001 Apr 4.
The Na(+)/I(-) symporter (NIS) is a key plasma membrane glycoprotein that mediates active I(-) transport in the thyroid gland (Dai, G., Levy, O., and Carrasco, N. (1996) Nature 379, 458-460), the first step in thyroid hormone biogenesis. Whereas relatively little is known about the mechanisms by which thyrotropin (TSH), the main hormonal regulator of thyroid function, regulates NIS activity, post-transcriptional events have been suggested to play a role (Kaminsky, S. M., Levy, O., Salvador, C., Dai, G., and Carrasco, N. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 3789-3793). Here we show that TSH induces de novo NIS biosynthesis and modulates the long NIS half-life ( approximately 5 days). In addition, we demonstrate that TSH is required for NIS targeting to or retention in the plasma membrane. We further show that NIS is a phosphoprotein and that TSH modulates its phosphorylation pattern. These results provide strong evidence of the major role played by post-transcriptional events in the regulation of NIS by TSH. Beyond their inherent interest, it is also of medical significance that these TSH-dependent regulatory mechanisms may be altered in the large proportion of thyroid cancers in which NIS is predominantly expressed in intracellular compartments, instead of being properly targeted to the plasma membrane.
钠/碘同向转运体（NIS）是一种关键的质膜糖蛋白，介导甲状腺中碘离子的主动转运（戴，G.，利维，O.，和卡拉斯科，N.（1996年）《自然》379，458 - 460），这是甲状腺激素生物合成的第一步。虽然对于甲状腺功能的主要激素调节因子促甲状腺激素（TSH）调节NIS活性的机制了解相对较少，但已有研究表明转录后事件发挥了作用（卡明斯基，S. M.，利维，O.，萨尔瓦多，C.，戴，G.，和卡拉斯科，N.（1994年）《美国国家科学院院刊》91，3789 - 3793）。在此我们表明，TSH诱导NIS的从头生物合成并调节其较长的半衰期（约5天）。此外，我们证明TSH对于NIS靶向质膜或保留在质膜中是必需的。我们进一步表明NIS是一种磷蛋白，并且TSH调节其磷酸化模式。这些结果为转录后事件在TSH对NIS的调节中所起的主要作用提供了有力证据。除了其内在的研究价值外，这些TSH依赖性调节机制在很大一部分甲状腺癌中可能发生改变，在这些甲状腺癌中NIS主要在细胞内区室表达，而不是正确靶向到质膜，这也具有医学意义。
