Differential Role of Serines and Threonines in Intracellular Loop 3 and C-Terminal Tail of the Histamine H₄ Receptor in β-Arrestin and G Protein-Coupled Receptor Kinase Interaction, Internalization, and Signaling.

ABSTRACT: The histamine H₄ receptor (H₄R) activates Gα_i-mediated signaling and recruits β-arrestin2 upon stimulation with histamine. β-Arrestins play a regulatory role in G protein-coupled receptor (GPCR) signaling by interacting with phosphorylated serine and threonine residues in the GPCR C-terminal tail and intracellular loop 3, resulting in receptor desensitization and internalization. Using bioluminescence resonance energy transfer (BRET)-based biosensors, we show that G protein-coupled receptor kinases (GRK) 2 and 3 are more quickly recruited to the H₄R than β-arrestin1 and 2 upon agonist stimulation, whereas receptor internalization dynamics toward early endosomes was slower. Alanine-substitution revealed that a serine cluster at the distal end of t

SUBMITTER: Verweij EWE 

PROVIDER: S-EPMC7155198 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature