Mechanisms of homologous and heterologous phosphorylation of FFA receptor 4 (GPR120): GRK6 and PKC mediate phosphorylation of Thr347, Ser350, and Ser357 in the C-terminal tail

摘要: Free fatty acid receptor 4 (FFA4), previously known as GPR120, is a G protein-coupled that promotes numerous anti-inflammatory and antidiabetic effects upon its agonism by long chained unsaturated acids. We have demonstrated of FFA4 with docosahexaenoic (DHA) alpha-linoleic (ALA) facilitates rapid transient phosphorylation expressed ectopically on the surface HEK293 cells. However, precise mechanisms promote remain elusive. In current study, we examined behind both heterologous homologous set out to identify foci phosphorylation. Our results demonstrate basal are mediated protein kinase C (PKC), while 6 (GRK6) plays predominant role in DHA-mediated FFA4. Furthermore, Thr(347), Ser(350), Ser(357) C-terminal tail major sites Concurrent mutation these three leads seemingly affects Gαq/11 signaling positive manner heightened intracellular Ca(2+) responses following DHA. Importantly, this phosphodefective mutant lacked ability β-arrestin-2 recruitment cell membrane. Since many functionally beneficial physiological noted be β-arrestin mediated, findings could provide insight into structural requirements for function.