Chemokine receptors are seven-transmembrane G-protein-coupled receptors (GPCRs). For most GPCRs, agonist-induced receptor phosphorylation at C-terminus leads to the recruitment of β-arrestins, resulting in receptor desensitization and internalization. CCR6 is a CC chemokine receptor whose ligand is CCL20. The role of site-specific phosphorylation of CCR6 at C-terminus in CCR6 biological function has not been investigated yet. In this study, we have intended to identify the specific serine/threonine residues at C-terminus of CCR6, and studied their role in the regulation of CCR6 biological function. We have generated a series of site-specific mutants in which specific serine/threonine residues at C-terminal tail of CCR6 were mutated into alanine as well as deletion mutants in which progressive truncation of C-terminus of CCR6 were generated. We have used these CCR6 mutants to characterize the role of site-specific serine/threonine residues in the regulation of CCR6 biology including the association of β-arrestins with CCR6, the internalization and desensitization of CCR6, the intracellular signaling of CCR6, the intracellular trafficking of CCR6, and the CCR6-mediated cell migration. We found that site-specific phosphorylation of threonine/serine residues at C-terminus of CCR6 differentially regulates CCR6 biological functions. The results will be presented and discussed.
- Copyright © 2013 by The American Association of Immunologists, Inc.