Agonist-induced phosphorylation of orthologues of the orphan receptor GPR35 functions as an activation sensor.

ABSTRACT: G protein-coupled receptor 35 (GPR35) is poorly characterized but nevertheless has been revealed to have diverse roles in areas including lower gut inflammation and pain. The development of novel reagents and tools will greatly enhance analysis of GPR35 functions in health and disease. Here, we used mass spectrometry, mutagenesis, and [³²P] orthophosphate labeling to identify that all five hydroxy-amino acids in the C-terminal tail of human GPR35a became phosphorylated in response to agonist occupancy of the receptor and that, apart from Ser²⁹⁴, each of these contributed to interactions with arretin-3, which inhibits further G protein-coupled receptor signaling. We found that Ser³⁰³ was key to such interactions; the serine corresponding to human GPR35a resi

SUBMITTER: Divorty N 

PROVIDER: S-EPMC8892012 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature