Disease relevance of CMKLR1

• In a panel of 27 HIV-1 isolates tested, 12 isolates could use CMKLR1/ChemR23 [1].
• Freshly isolated macrophages from human ascites fluid express CMKLR1 and are chemerin responsive, as well [2].
• Characterization of the human chemerin receptor - ChemR23/CMKLR1 - as co-receptor for human and simian immunodeficiency virus infection, and identification of virus-binding receptor domains [1].
• Given the increasing number of chemoattractant receptors used by HIV-1, HIV-2 and SIV as coreceptors, ChemR23 was tested in fusion assays for potential coreceptor activity by a range of viral strains [3].
• HHV-8-GPCR is a chemokine-like receptor encoded by KSHV, the etiologic agent of KS [4].

High impact information on CMKLR1

• Treatment of DCs with small interference RNA specific for ChemR23 sharply reduced RvE1 regulation of IL-12 [5].
• Chemerin was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner [6].
• ChemR23 is an orphan G protein-coupled receptor related to chemokine receptors, which is expressed specifically in these cell types [6].
• Activation of chemerin by the serine protease cascades that trigger rapid defenses in the body may direct CMKLR1-positive plasmacytoid dendritic cell and tissue macrophage recruitment to sterile sites of tissue damage, as well as trafficking to sites of infectious and allergic inflammation [7].
• We use a novel mAb specific for serpentine chemokine-like receptor 1 (CMKLR1) to evaluate its expression by circulating leukocytes in humans [8].

Biological context of CMKLR1

• To define the pathophysiologic triggers of chemerin activity, we evaluated the ability of serum- and inflammation-associated proteases to cleave chemerin and stimulate CMKLR1-mediated chemotaxis [7].
• We identify a major serum agonist activity for CMKLR1 as chemerin, a proteolytically activated attractant and the sole known ligand for CMKLR1, and we show that chemerin is activated during blood coagulation and attracts pDC but not mDC in ex vivo chemotaxis assays [8].
• The gene encoding ChemR23 was assigned by radiation hybrid mapping to the q21.2-21.3 region of human chromosome 12, outside the gene clusters identified so far for chemoattractant receptors [3].
• Using fluorescence in situ hybridization the gene encoding CMLKR1 (chemokine-like receptor 1) was localized to human chromosome 12q24.1 [9].
• Here we report the cloning of the mouse cmklr1 gene, the characterization of its genomic structure for comparison with the human gene, and the mapping and functional analysis of its 5' flanking sequence [10].

Anatomical context of CMKLR1

• We show that CMKLR1 is expressed by circulating pDCs in human blood, whereas myeloid DCs (mDCs) as well as lymphocytes, monocytes, neutrophils, and eosinophils are negative [8].
• OBJECTIVE: Chemokine-like receptor 1 (CMKLR1) is expressed by human antigen presenting cells and binds to chemerin, a proteolytically activatable chemoattractant [2].

Associations of CMKLR1 with chemical compounds

• We report the cloning of a novel human gene encoding an orphan receptor (ChemR23) related to the C3a, C5a and formyl Met-Leu-Phe receptors, and more distantly to the subfamilies of chemokine receptors [3].
• To address this concern, we used a biotin-avidin linkage to conjugate rAd vectors to ligands which bind with high affinity to selected receptors on DC (ChemR23, alpha(v)beta3 integrin, and DC-SIGN) [11].

Other interactions of CMKLR1

• We report the cloning of a novel human gene, CMKLR1, which encodes a protein that has notable sequence and structural homology to the seven transmembrane G-protein linked chemokine receptors [9].
• As expected from a relatively high sequence homology with the extracellular domains of CCR3, HIV-1 isolates showing R3 tropism were particularly efficient in using CMKLR1/ChemR23 [1].
• Bonzo, GPR1 and ChemR23 mRNAs were detected in all TC preparations [12].
• We have recently isolated a bioactive, circulating protein of human tazarotene-induced gene-2 (TIG2) as the natural ligand of the orphan receptor ChemR23 [13].

Analytical, diagnostic and therapeutic context of CMKLR1

• Molecular cloning of a novel receptor (CMKLR1) with homology to the chemotactic factor receptors [9].

References