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

Abstract

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