内皮素 B 型受体与 78kDa 葡萄糖调节蛋白相互作用。

Endothelin type B receptor interacts with the 78-kDa glucose-regulated protein.

机构信息

Department of Cellular Pharmacology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Department of Molecular Biology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

出版信息

FEBS Lett. 2019 Mar;593(6):644-651. doi: 10.1002/1873-3468.13347. Epub 2019 Mar 5.

DOI:10.1002/1873-3468.13347

PMID:30801683

Abstract

Endothelin (ET)-1 is involved in the vascular system, cell proliferation and apoptosis. ET receptors consist of ET type A receptor (ET R) and ET type B receptor (ET R). ET R and ET R generally exhibit opposite responses, although many exceptions exist. In the present study, we attempted to identify ET R- or ET R-specific binding proteins to understand the differences in ET R- and ET R-mediated responses after ET-1 stimulation. The 78-kDa glucose-regulated protein (GRP78) showed a stronger binding affinity towards ET R than towards ET R. Moreover, GRP78 overexpression promoted ET R-mediated ERK activation and GRP78 silencing suppressed ET R-mediated ERK activation. Furthermore, ET R can localize GRP78 to the cell periphery. These results suggest that the interaction of ET R with GRP78 affects ERK activation and GRP78 localization.

摘要

内皮素 (ET)-1 参与血管系统、细胞增殖和细胞凋亡。ET 受体包括 ET 型 A 受体 (ET R) 和 ET 型 B 受体 (ET R)。ET R 和 ET R 通常表现出相反的反应，尽管存在许多例外。在本研究中，我们试图鉴定 ET R 或 ET R 特异性结合蛋白，以了解 ET-1 刺激后 ET R 和 ET R 介导的反应的差异。78kDa 葡萄糖调节蛋白 (GRP78) 对 ET R 的结合亲和力强于对 ET R 的结合亲和力。此外，GRP78 过表达促进了 ET R 介导的 ERK 激活，而 GRP78 沉默抑制了 ET R 介导的 ERK 激活。此外，ET R 可以将 GRP78 定位到细胞外周。这些结果表明，ET R 与 GRP78 的相互作用影响 ERK 激活和 GRP78 定位。