Functional impact of intramolecular cleavage and dissociation of adhesion G protein-coupled receptor GPR133 (ADGRD1) on canonical signaling.

ABSTRACT: GPR133 (ADGRD1), an adhesion G protein-coupled receptor (GPCR) whose canonical signaling activates G_αS-mediated generation of cytosolic cAMP, has been shown to be necessary for the growth of glioblastoma (GBM), a brain malignancy. The extracellular N terminus of GPR133 is thought to be autoproteolytically cleaved into N-terminal and C- terminal fragments (NTF and CTF, respectively). However, the role of this cleavage in receptor activation remains unclear. Here, we used subcellular fractionation and immunoprecipitation approaches to show that the WT GPR133 receptor is cleaved shortly after protein synthesis and generates significantly more canonical signaling than an uncleavable point mutant GPR133 (H543R) in patient-derived GBM cultures and HEK293T cells. After cleavage, the re

SUBMITTER: Frenster JD 

PROVIDER: S-EPMC8215292 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature