G protein-coupled receptor kinase phosphorylation of distal C-tail sites specifies βarrestin1-mediated signaling by chemokine receptor CXCR4. J Biol Chem 2022 Sep;298(9):102351
Date
08/09/2022Pubmed ID
35940305Pubmed Central ID
PMC9465349DOI
10.1016/j.jbc.2022.102351Scopus ID
2-s2.0-85137163299 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
G protein-coupled receptor (GPCR) kinases (GRKs) and arrestins mediate GPCR desensitization, internalization, and signaling. The spatial pattern of GPCR phosphorylation is predicted to trigger these discrete GRK and arrestin-mediated functions. Here, we provide evidence that distal carboxyl-terminal tail (C-tail), but not proximal, phosphorylation of the chemokine receptor CXCR4 specifies βarrestin1 (βarr1)-dependent signaling. We demonstrate by pharmacologic inhibition of GRK2/3-mediated phosphorylation of the chemokine receptor CXCR4 coupled with site-directed mutagenesis and bioluminescence resonance energy transfer approaches that distal, not proximal, C-tail phosphorylation sites are required for recruitment of the adaptor protein STAM1 (signal-transducing adaptor molecule) to βarr1 and focal adhesion kinase phosphorylation but not extracellular signal-regulated kinase 1/2 phosphorylation. In addition, we show that GPCRs that have similarly positioned C-tail phosphoresidues are also able to recruit STAM1 to βarr1. However, although necessary for some GPCRs, we found that distal C-tail sites might not be sufficient to specify recruitment of STAM1 to βarr1 for other GPCRs. In conclusion, this study provides evidence that distal C-tail phosphorylation sites specify GRK-βarrestin-mediated signaling by CXCR4 and other GPCRs.
Author List
Zhuo Y, Crecelius JM, Marchese AAuthor
Adriano Marchese PhD Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ArrestinArrestins
G-Protein-Coupled Receptor Kinases
Phosphorylation
beta-Arrestin 1
beta-Arrestins
