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

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.