Type I angiotensin II receptor-associated protein ARAP1 binds and recycles the receptor to the plasma membrane
Type I angiotensin II receptor-associated protein ARAP1 binds and recycles the receptor to the plasma membrane
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DOI：
10.1016/j.bbrc.2003.09.154
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发表时间：
2003-10-31
影响因子：
3.1
通讯作者：
Inagami, T
中科院分区：
文献类型：
--
作者：
Guo, DF;Chenier, I;Inagami, T
I型血管紧张素II受体（AT）的羧基末端在受体磷酸化、脱敏和内化中起重要作用。利用酵母双杂交系统分离AT（1A）受体羧基端相关蛋白。在本研究中，我们报告了一种新的蛋白质ARAP 1的分离，它可以促进AT（1A）在HEK-293细胞中向质膜的再循环。ARAP 1 cDNA编码493个氨基酸的蛋白质，其mRNA在大鼠组织中广泛表达。免疫共沉淀和Western blotting检测到ARAP 1与AT（1A）在HEK-293细胞中形成复合物。在ARAP 1的存在下，回收的AT（1A）在第一次处理后30 min对Ang II的第二次刺激显示出显著的Ca 2+释放反应。免疫细胞化学分析显示，再循环的AT（1A）和ARAP 1的共同定位在质膜后45分钟，首次暴露于Ang II。总之，这些结果表明ARAP 1在AT 1受体再循环至质膜中的作用，推测伴随着受体信号功能的恢复。(C)2003年爱思唯尔公司All rights reserved.
The carboxyl terminus of the type I angiotensin II receptor (AT,) plays an important role in receptor phosphorylation, desensitization, and internalization. The yeast two-hybrid system was employed to isolate proteins associated with the carboxyl terminal region of the AT(1A) receptor. In the present study, we report the isolation of a novel protein, ARAP1, which promotes recycling of AT(1A) to the plasma membrane in HEK-293 cells. ARAP1 cDNA encodes a 493-amino-acid protein and its mRNA is ubiquitously expressed in rat tissues. A complex of ARAP1 and AT(1A) was observed by immunoprecipitation and Western blotting in HEK-293 cells. In the presence of ARAP1, recycled AT(1A) showed a significant Ca2+ release response to a second stimulation by Ang II 30 min after the first treatment. Immunocytochemical analysis revealed co-localization of recycled AT(1A) and ARAP1 in the plasma membrane 45 min after the initial exposure to Ang II. Taken together, these results indicate a role for ARAP1 in the recycling of the AT, receptor to the plasma membrane with presumable concomitant recovery of receptor signal functions. (C) 2003 Elsevier Inc. All rights reserved.