Linkage of the ubiquitin-conjugating system and the endocytic pathway in ligand-induced internalization of the growth hormone receptor
Linkage of the ubiquitin-conjugating system and the endocytic pathway in ligand-induced internalization of the growth hormone receptor
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DOI：
10.1093/emboj/16.16.4851
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发表时间：
1997-08-15
期刊：
影响因子：
11.4
通讯作者：
Strous, GJ
中科院分区：
文献类型：
--
作者：
Govers, R;vanKerkhof, P;Strous, GJ
泛素结合系统的主要功能是靶向胞浆和核蛋白，使其被蛋白酶体降解。最近，泛素结合参与了酵母中信号受体如哺乳动物生长激素受体(GHR)和α-因子受体的下调。通过研究截断的受体、内化缺陷受体突变体F327A和笼蛋白介导的GHR内吞被抑制的条件，我们证明了GHR泛素化和配体诱导的GHR内化是耦合的事件。以前，我们已经证明GHR的内吞依赖于完整的泛素化系统，我们的证据表明，泛素结合系统和内吞途径在GHR的胞膜尾部相互作用。在那里，他们合作监管GHR的内部化。
The major function of the ubiquitin-conjugating system is the targeting of cytosolic and nuclear proteins for degradation by the proteasome. Recently, ubiquitin conjugation has been implicated in the downregulation of signalling receptors such as the mammalian growth hormone receptor (GHR) and the alpha-factor receptor in yeast, By examining truncated receptors, the internalization-deficient receptor mutant F327A and conditions under which clathrin-mediated GHR endocytosis is inhibited, we show here that GHR ubiquitination and ligand-induced GHR internalization are coupled events, Previously, we had shown that GHR endocytosis is dependent on an intact ubiquitination system, Here we present evidence that GHR ubiquitination depends on an intact endocytic pathway, Our data indicate that the ubiquitin-conjugating system and the endocytic pathway interact at the cytoplasmic tail of the GHR at the plasma membrane, where they cooperate to regulate internalization of the GHR.