Mechanisms of Regulation of the Chemokine-Receptor Network.
The interactions of chemokines with their G protein-coupled receptors promote the migration of leukocytes during normal immune function and as a key aspect of the inflammatory response to tissue injury or infection. This review summarizes the major cellular and biochemical mechanisms by which the interactions of chemokines with chemokine receptors are regulated, including: selective and competitive binding interactions; genetic polymorphisms; mRNA splice variation; variation of expression, degradation and localization; down-regulation by atypical (decoy) receptors; interactions with cell-surface glycosaminoglycans; post-translational modifications; oligomerization; alternative signaling responses; and binding to natural or pharmacological inhibitors.
Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. martin.stone@monash.edu.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia. martin.stone@monash.edu.
Martin J
MJ
Stone
Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. jenni.hayward@monash.edu.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia. jenni.hayward@monash.edu.
Jenni A
JA
Hayward
Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. cheng.huang@monash.edu.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia. cheng.huang@monash.edu.
Cheng
C
Huang
Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. zil.huma@monash.edu.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia. zil.huma@monash.edu.
Zil
Z
E Huma
Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. julie.sanchez@monash.edu.|Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia. julie.sanchez@monash.edu.
Julie
J
Sanchez
D000818:Animals; D001667:Binding, Competitive; D018925:Chemokines / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D005810:Multigene Family; D011110:Polymorphism, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D059748:Proteolysis; D012326:RNA Splicing; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
D018925:Chemokines; D006025:Glycosaminoglycans; D008024:Ligands; D019707:Receptors, Chemokine
binding; chemokine; chemokine receptor; expression; glycosaminoglycan; inhibitor; oligomerization; post-translational modification; regulation; signaling