Key phosphorylation sites in GPCRs orchestrate the contribution of ?-Arrestin 1 in ERK1/2 activation

ABSTRACT: ?-arrestins (?arrs) are key regulators of GPCR signaling and trafficking, and their knockdown typically leads to a decrease in agonist-induced ERK1/2 MAP kinase activation. Interestingly, for some GPCRs, knockdown of ?arr1 augments agonist-induced ERK1/2 phosphorylation although a mechanistic basis for this intriguing phenomenon is unclear. Here, we use selected GPCRs to explore a possible correlation between the spatial positioning of receptor phosphorylation sites and the contribution of ?arr1 in ERK1/2 activation. We discover that engineering a spatially positioned double-phosphorylation-site cluster in the bradykinin receptor (B2R), analogous to that present in the vasopressin receptor (V2R), reverses the contribution of ?arr1 in ERK1/2 activation from inhibitory to promotive. An intra

SUBMITTER: Prof. Arun, Kumar Shukla 

PROVIDER: S-SCDT-EMBOR-2019-49886V1P | biostudies-other |

REPOSITORIES: biostudies-other