Atypical Chemokine Receptor 3 'Senses' CXC Chemokine Receptor 4 Activation Through GPCR Kinase Phosphorylation.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
10 Mar 2023
10 Mar 2023
Historique:
pubmed:
4
3
2023
medline:
4
3
2023
entrez:
3
3
2023
Statut:
epublish
Résumé
Atypical chemokine receptor 3 (ACKR3) is an arrestin-biased receptor that regulates extracellular chemokine levels through scavenging. The scavenging action mediates the availability of the chemokine CXCL12 for the G protein-coupled receptor (GPCR) CXCR4 and requires phosphorylation of the ACKR3 C-terminus by GPCR kinases (GRKs). ACKR3 is phosphorylated by GRK2 and GRK5, but the mechanisms by which these kinases regulate the receptor are unresolved. Here we mapped the phosphorylation patterns and determined that GRK5 phosphorylation of ACKR3 dominates β-arrestin recruitment and chemokine scavenging over GRK2. Co-activation of CXCR4 significantly enhanced phosphorylation by GRK2 through the liberation of Gβγ. These results suggest that ACKR3 'senses' CXCR4 activation through a GRK2-dependent crosstalk mechanism. Surprisingly, we also found that despite the requirement for phosphorylation, and the fact that most ligands promote β-arrestin recruitment, β-arrestins are dispensable for ACKR3 internalization and scavenging, suggesting a yet to be determined function for these adapter proteins.
Identifiants
pubmed: 36865154
doi: 10.1101/2023.02.25.530029
pmc: PMC9980177
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : R01 CA221289
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA254402
Pays : United States
Organisme : NIGMS NIH HHS
ID : F32 GM137505
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM133157
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI161880
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL071818
Pays : United States
Commentaires et corrections
Type : UpdateIn
Références
Sci Signal. 2011 Aug 9;4(185):ra51
pubmed: 21868357
J Biol Chem. 1996 Oct 4;271(40):24907-13
pubmed: 8798768
Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):E5363-72
pubmed: 25468967
J Biol Chem. 2018 Jan 19;293(3):893-905
pubmed: 29180449
Cell Mol Neurobiol. 2013 Jan;33(1):111-8
pubmed: 22940879
Nat Cell Biol. 2020 Mar;22(3):266-273
pubmed: 32042179
Curr Protoc Pharmacol. 2014 Dec 01;67:2.11.1-2.11.19
pubmed: 25446290
Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2985-90
pubmed: 9501202
Nat Commun. 2022 Jan 25;13(1):487
pubmed: 35078997
Nat Commun. 2017 Jan 18;8:14135
pubmed: 28098154
Sci Signal. 2019 Sep 10;12(598):
pubmed: 31506383
Nat Commun. 2018 Jan 23;9(1):341
pubmed: 29362459
J Exp Med. 2006 Sep 4;203(9):2201-13
pubmed: 16940167
Methods Enzymol. 2016;570:233-60
pubmed: 26921949
Nat Rev Immunol. 2013 Nov;13(11):815-29
pubmed: 24319779
J Leukoc Biol. 2016 Jun;99(6):883-92
pubmed: 26740381
Methods Enzymol. 2013;521:347-66
pubmed: 23351749
Annu Rev Immunol. 2014;32:659-702
pubmed: 24655300
J Biol Chem. 2007 Dec 21;282(51):36971-9
pubmed: 17947233
Mol Cell. 2021 Nov 18;81(22):4605-4621.e11
pubmed: 34582793
J Med Chem. 2008 Dec 25;51(24):7915-20
pubmed: 19053768
J Biol Chem. 1998 Nov 20;273(47):31510-8
pubmed: 9813065
Glia. 2012 Mar;60(3):372-81
pubmed: 22083878
Cell Rep. 2019 Feb 5;26(6):1473-1488.e9
pubmed: 30726732
Sci Adv. 2022 Jul 15;8(28):eabn8063
pubmed: 35857509
Curr Biol. 2007 Jun 19;17(12):1026-31
pubmed: 17570670
PLoS One. 2012;7(3):e34192
pubmed: 22457824
Oncogene. 2010 Aug 12;29(32):4599-610
pubmed: 20531309
Front Immunol. 2020 Apr 22;11:720
pubmed: 32391018
Annu Rev Biophys. 2017 May 22;46:175-198
pubmed: 28532213
Nat Commun. 2022 Jan 27;13(1):540
pubmed: 35087057
Nat Protoc. 2006;1(1):241-5
pubmed: 17406239
Sci Rep. 2020 Oct 15;10(1):17395
pubmed: 33060647
Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14759-64
pubmed: 17804806
Trends Pharmacol Sci. 2018 May;39(5):481-493
pubmed: 29548548
J Biol Chem. 2011 Sep 16;286(37):32188-97
pubmed: 21730065
Science. 1992 Aug 28;257(5074):1264-7
pubmed: 1325672
Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):628-32
pubmed: 20018651
J Biol Chem. 1994 Feb 25;269(8):6193-7
pubmed: 8119963
Protein Expr Purif. 2020 Apr;168:105547
pubmed: 31786308
Front Cell Dev Biol. 2021 May 24;9:687489
pubmed: 34109182
Biochemistry. 2005 May 10;44(18):6958-70
pubmed: 15865441
J Neuroimmunol. 2008 Jul 31;198(1-2):9-13
pubmed: 18533280
J Biol Chem. 1994 Jan 7;269(1):37-40
pubmed: 8276821
J Biol Chem. 1993 Apr 15;268(11):8256-60
pubmed: 8463335
Sci Signal. 2023 Jan 31;16(770):eabo4314
pubmed: 36719944
J Biol Chem. 2012 Aug 17;287(34):28362-77
pubmed: 22736769
Cell. 2008 Feb 8;132(3):463-73
pubmed: 18267076
Cells. 2021 Mar 11;10(3):
pubmed: 33799570
J Biol Chem. 2005 Oct 21;280(42):35760-6
pubmed: 16107333
Nat Commun. 2020 Sep 25;11(1):4855
pubmed: 32978390
Sci Rep. 2021 Feb 9;11(1):3426
pubmed: 33564089
Dev Cell. 2020 Feb 24;52(4):492-508.e10
pubmed: 32059773
J Biol Chem. 1994 Apr 8;269(14):10209-12
pubmed: 8144599
Nat Commun. 2016 Jul 11;7:12178
pubmed: 27397672
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17789-94
pubmed: 17095603
Oncogene. 2012 Nov 8;31(45):4750-8
pubmed: 22266857
J Biol Chem. 2010 Mar 5;285(10):7805-17
pubmed: 20048153