PMID- 23408426
OWN - NLM
STAT- MEDLINE
DCOM- 20130531
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 288
IP  - 14
DP  - 2013 Apr 5
TI  - Tyrosine sulfation of chemokine receptor CCR2 enhances interactions with both 
      monomeric and dimeric forms of the chemokine monocyte chemoattractant protein-1 
      (MCP-1).
PG  - 10024-10034
LID - S0021-9258(20)67362-8 [pii]
LID - 10.1074/jbc.M112.447359 [doi]
AB  - Chemokine receptors are commonly post-translationally sulfated on tyrosine 
      residues in their N-terminal regions, the initial site of binding to chemokine 
      ligands. We have investigated the effect of tyrosine sulfation of the chemokine 
      receptor CCR2 on its interactions with the chemokine monocyte chemoattractant 
      protein-1 (MCP-1/CCL2). Inhibition of CCR2 sulfation, by growth of expressing 
      cells in the presence of sodium chlorate, significantly reduced the potency for 
      MCP-1 activation of CCR2. MCP-1 exists in equilibrium between monomeric and 
      dimeric forms. The obligate monomeric mutant MCP-1(P8A) was similar to wild type 
      MCP-1 in its ability to induce leukocyte recruitment in vivo, whereas the 
      obligate dimeric mutant MCP-1(T10C) was less effective at inducing leukocyte 
      recruitment in vivo. In two-dimensional NMR experiments, sulfated peptides 
      derived from the N-terminal region of CCR2 bound to both the monomeric and 
      dimeric forms of wild type MCP-1 and shifted the equilibrium to favor the 
      monomeric form. Similarly, MCP-1(P8A) bound more tightly than MCP-1(T10C) to the 
      CCR2-derived sulfopeptides. NMR chemical shift mapping using the MCP-1 mutants 
      showed that the sulfated N-terminal region of CCR2 binds to the same region 
      (N-loop and beta3-strand) of both monomeric and dimeric MCP-1 but that binding to 
      the dimeric form also influences the environment of chemokine N-terminal 
      residues, which are involved in dimer formation. We conclude that interaction 
      with the sulfated N terminus of CCR2 destabilizes the dimerization interface of 
      inactive dimeric MCP-1, thus inducing dissociation to the active monomeric state.
FAU - Tan, Joshua H Y
AU  - Tan JHY
AD  - Department of Biochemistry and Molecular Biology, Monash University, Clayton, 
      Victoria 3800, Australia.
FAU - Ludeman, Justin P
AU  - Ludeman JP
AD  - Department of Biochemistry and Molecular Biology, Monash University, Clayton, 
      Victoria 3800, Australia.
FAU - Wedderburn, Jamie
AU  - Wedderburn J
AD  - Department of Biochemistry and Molecular Biology, Monash University, Clayton, 
      Victoria 3800, Australia.
FAU - Canals, Meritxell
AU  - Canals M
AD  - Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash 
      University, Parkville, Victoria 3052, Australia.
FAU - Hall, Pam
AU  - Hall P
AD  - Centre for Inflammatory Diseases, Monash University, Department of Medicine, 
      Monash Medical Centre, Clayton, Victoria 3168, Australia.
FAU - Butler, Stephen J
AU  - Butler SJ
AD  - School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, 
      Australia.
FAU - Taleski, Deni
AU  - Taleski D
AD  - School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, 
      Australia.
FAU - Christopoulos, Arthur
AU  - Christopoulos A
AD  - Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash 
      University, Parkville, Victoria 3052, Australia.
FAU - Hickey, Michael J
AU  - Hickey MJ
AD  - Centre for Inflammatory Diseases, Monash University, Department of Medicine, 
      Monash Medical Centre, Clayton, Victoria 3168, Australia.
FAU - Payne, Richard J
AU  - Payne RJ
AD  - School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, 
      Australia.
FAU - Stone, Martin J
AU  - Stone MJ
AD  - Department of Biochemistry and Molecular Biology, Monash University, Clayton, 
      Victoria 3800, Australia. Electronic address: martin.stone@monash.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130213
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chemokine CCL2)
RN  - 0 (Peptides)
RN  - 0 (Receptors, CCR2)
RN  - 42HK56048U (Tyrosine)
RN  - 70FD1KFU70 (Sulfur)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - SY7Q814VUP (Calcium)
SB  - IM
EIN - J Biol Chem. 2014 May 9;289(19):13362
MH  - Binding Sites
MH  - Calcium/metabolism
MH  - Chemokine CCL2/*metabolism
MH  - Dimerization
MH  - *Gene Expression Regulation
MH  - HEK293 Cells
MH  - Humans
MH  - Kinetics
MH  - Magnetic Resonance Spectroscopy/methods
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Models, Chemical
MH  - Peptides/chemistry
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Processing, Post-Translational
MH  - Receptors, CCR2/*chemistry/physiology
MH  - Sulfur/chemistry
MH  - Tyrosine/*chemistry
PMC - PMC3617241
EDAT- 2013/02/15 06:00
MHDA- 2013/06/01 06:00
PMCR- 2014/04/05
CRDT- 2013/02/15 06:00
PHST- 2013/02/15 06:00 [entrez]
PHST- 2013/02/15 06:00 [pubmed]
PHST- 2013/06/01 06:00 [medline]
PHST- 2014/04/05 00:00 [pmc-release]
AID - S0021-9258(20)67362-8 [pii]
AID - M112.447359 [pii]
AID - 10.1074/jbc.M112.447359 [doi]
PST - ppublish
SO  - J Biol Chem. 2013 Apr 5;288(14):10024-10034. doi: 10.1074/jbc.M112.447359. Epub 
      2013 Feb 13.