Wruck Christoph J, Funke-Kaiser Heiko, Pufe Thomas, Kusserow Heike, Menk Mario, Schefe Jan H, Kruse Marie L, Stoll Monika, Unger Thomas
Institute of Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):57-64. doi: 10.1161/01.ATV.0000150662.51436.14. Epub 2004 Nov 11.
Synthesis and maturation of G protein-coupled receptors are complex events that require an intricate combination of processes including protein folding, posttranslational modifications, and transport through distinct cellular compartments. Little is known concerning the regulation of G protein-coupled receptor transport from the endoplasmic reticulum to the cell surface.
Here we show that the cytoplasmatic carboxy-terminal of the angiotensin AT2 receptor (AT2R) acts independently as an endoplasmic reticulum-export signal. Using a yeast two-hybrid system, we identified a Golgi membrane-associated protein termed ATBP50 (for AT2R binding protein of 50 kDa) that binds to this motif. We also cloned ATBP60 and ATBP135 encoded by the same gene as ATBP50 that mapped to chromosomes 8p21.3. Downregulation of ATBP50 using siRNA leads to retention of AT2R in inner compartments, reduced cell surface expression, and decreased antiproliferative effects of the receptor.
Our results indicate that ATBP50 regulates the transport of the AT2R to cell membrane by binding to a specific motif within its cytoplasmic carboxy-terminal and thereby enabling the antiproliferative effects of the receptor.
G蛋白偶联受体的合成与成熟是复杂的过程，需要蛋白质折叠、翻译后修饰以及通过不同细胞区室运输等多种过程的复杂组合。关于G蛋白偶联受体从内质网到细胞表面的运输调控知之甚少。
在此我们表明，血管紧张素AT2受体（AT2R）的细胞质羧基末端独立作为内质网输出信号。利用酵母双杂交系统，我们鉴定出一种与高尔基体膜相关的蛋白，称为ATBP50（50 kDa的AT2R结合蛋白），它与该基序结合。我们还克隆了与ATBP50由同一基因编码的ATBP60和ATBP135，该基因定位于染色体8p21.3。使用小干扰RNA下调ATBP50会导致AT2R在内质网区室中滞留，细胞表面表达降低，以及该受体的抗增殖作用减弱。
我们的结果表明，ATBP50通过与AT2R细胞质羧基末端的特定基序结合来调节其向细胞膜的运输，从而实现该受体的抗增殖作用。
