Lydon J P, Power R F, Conneely O M
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Gene Expr. 1992;2(3):273-83.
We report that three orphan receptors, hERR1, hERR2, and hTR2, members of the steroid/thyroid receptor (SR/TR) superfamily, can be activated by different ligand-independent pathways. hERR1 and hERR2 exhibit constitutive activity in the absence of exogenously added ligands. Furthermore, this constitutive activity is localized in the carboxy terminal domain of both receptors and can be transferred to other members of this superfamily using domain switch strategies. In addition, we show that hERR1 can remain constitutively active in the less evolved eukaryotic cell Saccharomyces cerevisiae. In contrast, hTR2 is not constitutively active. However, a chimera of hTR2 can be activated in a ligand-independent manner through a signal transduction pathway initiated at the cell membrane by the neurotransmitter dopamine. Like hERR1 and hERR2, hTR2 is ligand-independently activated through its carboxy terminal domain. Together, these results suggest the existence of emerging subgroups within the SR/TR superfamily that can regulate gene expression through different modes of activation.
我们报告称，类固醇/甲状腺受体（SR/TR）超家族的三个孤儿受体hERR1、hERR2和hTR2可通过不同的非配体依赖性途径被激活。hERR1和hERR2在未添加外源配体的情况下表现出组成性活性。此外，这种组成性活性定位于这两个受体的羧基末端结构域，并且可以使用结构域切换策略转移到该超家族的其他成员中。此外，我们表明hERR1在进化程度较低的真核细胞酿酒酵母中可保持组成性活性。相比之下，hTR2没有组成性活性。然而，hTR2的嵌合体可通过神经递质多巴胺在细胞膜上启动的信号转导途径以非配体依赖性方式被激活。与hERR1和hERR2一样，hTR2通过其羧基末端结构域被非配体依赖性激活。总之，这些结果表明SR/TR超家族中存在新兴的亚组，它们可以通过不同的激活模式调节基因表达。
