GRK phosphorylation drives β-arrestin-independent internalization of chemokine receptor CXCR5.

ABSTRACT: G protein-coupled receptor kinases (GRKs) and β-arrestins act in concert to regulate G protein-coupled receptor signaling and trafficking. Previously, we showed that β-arrestins are essential for desensitization, but not internalization, of the chemokine receptor CXCR5. Here, we investigated the role of GRKs on β-arrestin recruitment, phosphorylation, and internalization of CXCR5 using gene-edited HEK293 cells in which the ubiquitously expressed GRKs have been deleted (GRK2/3/5/6; ΔQ-GRK). Using novel phospho-site-specific antibodies, we demonstrate that CXCL13 stimulation promotes rapid and sustained phosphorylation of the carboxyl terminal region (C-tail) of CXCR5 at paired Ser³⁶⁷Thr³⁶⁸ and Ser³⁷⁰Ser³⁷¹ residues, which we have previously shown

SUBMITTER: Crecelius JM 

PROVIDER: S-EPMC12859505 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature