Role and modulation of G protein-coupled receptor signaling in inflammatory processes.
Many extracellular stimuli, such as neurotransmitters, hormones, chemokines, proteinases, inflammatory mediators, odorants, and light, are recognized by the superfamily of G protein-coupled receptors (GPCRs). Immune cells express GPCRs for classical chemoattractants, chemokines, neuropeptides, and neurotransmitters. GPCRs transmit information by interacting with heterotrimeric G proteins, resulting in rapid and transient signaling. The signal given by GPCRs is terminated rapidly by the activity of regulators of G protein signaling (RGS). In addition, GPCR responsiveness diminishes after repeated or prolonged exposure to the agonist. This process of homologous desensitization of GPCRs is dependent on receptor phosphorylation by G protein-coupled receptor kinases (GRKs). In this review, we describe the role of RGS and GRKs in the regulation of GPCR signaling in the immune system, with special emphasis on the role of changes in GRKs and RGS expression during (auto) immune processes. Since altered regulation of GPCR signaling can influence disease states, the molecules involved in this process can also represent attractive therapeutic targets.
Lombardi
Maria Stella
MS
Department of Immunology, University Medical Center Utrecht, The Netherlands. m.s.lombardi@wkz.azu.nl
Kavelaars
Annemieke
A
Heijnen
Cobi J
CJ
D000818:Animals; D019390:Arrestins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005544:Forecasting; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
D019390:Arrestins; D011956:Receptors, Cell Surface; D011494:Protein Kinases; D019204:GTP-Binding Proteins