The G-protein coupled receptor CMKLR1/ChemR23: Studies on gene regulation, receptor ligand activation, and HIV/SIV co-receptor function
type: CreativeWork
description: In all higher organisms, there is a need for intercellular communication. G-protein coupled receptors (GPCRs), located on the cell surface, play an important role in this communication. Cells synthesize and release signalling molecules (ligands), which produce a specific response only in those cells that have a receptor for that ligand. The total number of GPCRs is estimated to be around 800 where approximately 160 still are "orphans", meaning that the endogenous ligands are unknown. CMKLR1/ChemR23 is a GPCR that was recently "de-orphanized" when the endogenous ligand, TIG2/chemerin, was isolated from inflammatory fluids and hemofiltrate. The receptor displays a high homology to chemoattractant-like receptors involved in inflammation processes. Sequence is implicated in osseous and cartilage development, and the receptor is also suggested to have a pathophysiological role as one of the co-receptors involved in human and simian immunodeficiency virus (HIV-1 and SIV)-infection of CD4+ immune cells. We have described the genomic organization of cmklr1 in mouse and analysed the regulatory mechanism behind the corresponding receptor expression. Two transcripts of mouse cmklr1 have been identified, cmklr1a and b, which utilize alternative promoters for transcription. We show that four Sp1 transcription factors are involved in cmklr1a promoter activation in mouse NB4 1A3 cells, whereas the transcription factor NFY is important for transcription of cmklr1b in mouse BV2 cells. Cmklr1a shows expression in organs such as heart and lung whereas cmklr1b is suggested to be an inducible transcript up-regulated by stimulation with all-trans retinoic acid (ATRA). The interaction between CMKLR1/ChemR23 and TIG2/chemerin in mouse has been studied. Mouse TIG2/chemerin was found to activate the mouse receptor, although to a lower degree than for the human receptor. Peptides corresponding to the C-terminus of mouse TIG2/chemerin could activate mouse CMKLR1/ChemR23 but to a lower extent t…
abstract: In all higher organisms, there is a need for intercellular communication. G-protein coupled receptors (GPCRs), located on the cell surface, play an important role in this communication. Cells synthesize and release signalling molecules (ligands), which produce a specific response only in those cells that have a receptor for that ligand. The total number of GPCRs is estimated to be around 800 where approximately 160 still are "orphans", meaning that the endogenous ligands are unknown. CMKLR1/ChemR23 is a GPCR that was recently "de-orphanized" when the endogenous ligand, TIG2/chemerin, was isolated from inflammatory fluids and hemofiltrate. The receptor displays a high homology to chemoattractant-like receptors involved in inflammation processes. Sequence is implicated in osseous and cartilage development, and the receptor is also suggested to have a pathophysiological role as one of the co-receptors involved in human and simian immunodeficiency virus (HIV-1 and SIV)-infection of CD4+ immune cells. We have described the genomic organization of cmklr1 in mouse and analysed the regulatory mechanism behind the corresponding receptor expression. Two transcripts of mouse cmklr1 have been identified, cmklr1a and b, which utilize alternative promoters for transcription. We show that four Sp1 transcription factors are involved in cmklr1a promoter activation in mouse NB4 1A3 cells, whereas the transcription factor NFY is important for transcription of cmklr1b in mouse BV2 cells. Cmklr1a shows expression in organs such as heart and lung whereas cmklr1b is suggested to be an inducible transcript up-regulated by stimulation with all-trans retinoic acid (ATRA). The interaction between CMKLR1/ChemR23 and TIG2/chemerin in mouse has been studied. Mouse TIG2/chemerin was found to activate the mouse receptor, although to a lower degree than for the human receptor. Peptides corresponding to the C-terminus of mouse TIG2/chemerin could activate mouse CMKLR1/ChemR23 but to a lower extent t…
author: Mårtensson, Ulrika
language: eng
keywords: Pharmacology and Toxicology, Medicin (människa och djur), Medicine (human and vertebrates), HIV/SIV, TIG2/chemerin, transcriptional regulation, ligand activation, Co-receptor, GPCR, ChemR23/CMKLR1
date published: 2005
date modified: 2026-07-24T03:00:02Z
provider: University of Lund
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Elsevier