CCR-L2 Membrane Protein Introduction

Introduction of CCR-L2

CCR-L2, alternatively known as chemokine receptor CCR11 or putative MCP-1 chemokine receptor, is in human encoded by CCRL2 gene. It is supposed to be a non-signaling seven transmembrane (7-TMD) protein and is related to the atypical chemokine receptor (ACKR) family. The ligands of CCR-L2 have been identified to be CCL19 and chemerin/RARRES2. CCR-L2 is highly expressed in primary neutrophils and primary monocytes and is further increased during monocyte to macrophage differentiation and neutrophil activation.

Basic Information of CCR-L2
Protein Name C-C chemokine receptor-like 2
Gene Name CCR-L2
Aliases Chemokine receptor CCR11, Chemokine receptor X, Putative MCP-1 chemokine receptor
Organism Homo sapiens (Human)
UniProt ID O00421
Transmembrane Times 7
Length (aa) 356

Function of CCR-L2 Membrane Protein

The signal transduction mediated by chemokines and their receptors are crucial for the recruitment of effector immune cells to the site of inflammation. However, CCR-L2 seems not to be a signaling receptor. CCRL2 does not trigger classic G protein-mediated signaling or mediate cell migration. It is supposed to function as a chemerin presenting molecule at the surface of barrier cells and may play a role in regulating chemokine-triggered immune responses by capturing and internalizing CCL19, or by presenting RARRES2 ligand to CMKLR1, which is a functional signaling receptor. This receptor may also contribute to the development of Th2 responses. A recent study has suggested supporting the proposed function of CCR-L2 as a chemerin anchoring protein on the surface of endothelial cells. Moreover, CCR-L2 also shows a pro-tumoral effect, which indicates the requirement of further investigations into the potential roles of CCRL2 as a novel therapeutic target and biomarker.

CCR L2 Membrane Protein IntroductionFig.1 Schematic drawing depicting the 7 helices, the connecting loops and some conserved amino acid motifs in GPCRs. (Veulens, 2009)

Application of CCR-L2 Membrane Protein in Literature

1. Reyes N., et al. Atypical chemokine receptor CCRL2 is overexpressed in prostate cancer cells. J Biomed Res. 2017. PubMed ID: 29497024

This article evaluates the differential expression of atypical receptor family in prostate cancer using quantitative PCR and further evaluation of CCRL2 at the protein level, which suggests its overexpression in a metastatic cell line and in malignant prostatic tissues from patients.

2. Malik F., et al. Chemokine (C-C Motif) Receptor-Like 2 is not essential for lung injury, lung inflammation, or airway hyperresponsiveness induced by acute exposure to ozone. Physiol Rep. 2017, 5(24). PubMed ID: 29242308

This article reveals that CCRL2 modulates chemerin levels in the epithelial lining fluid of the lungs but does not contribute to the development of O3-induced lung pathology.

3. Regan-Komito D., et al. Absence of the Non-Signalling Chemerin Receptor CCRL2 Exacerbates Acute Inflammatory Responses In Vivo. Front Immunol. 2017, 8: 1621. PubMed ID: 29209334

Authors in this group indicated that the absence of CCRL2 leads to increased levels of local and systemic chemerin levels and exacerbated inflammatory responses during an acute inflammatory challenge. These findings further highlight the importance of chemerin as a therapeutic target in inflammatory diseases.

4. Mazzotti C., et al. The Atypical Receptor CCRL2 (C-C Chemokine Receptor-Like 2) Does Not Act As a Decoy Receptor in Endothelial Cells. Front Immunol. 2017, 8:1233. PubMed ID: 29056935

This article focuses on identifying unique functional properties for CCRL2 of the non-signaling 7-TMD receptor family, which only recognized ligand, but excluded the ability of CCRL2 to perform scavenging.

5. Del Prete A., et al. The atypical receptor CCRL2 is required for CXCR2-dependent neutrophil recruitment and tissue damage. Blood. 2017, 130(10): 1223-1234. PubMed ID: 28743719

This article evaluates the biological role of CCRL2 in immunity and shows that upregulation of CCRL2 observed under inflammatory conditions is functional to finely tune CXCR2-mediated neutrophil recruitment at sites of inflammation.

CCR-L2 Preparation Options

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  1. Veulens A and Rodríguez R. (2009). Protein-coupled receptors as targets for drug design. Biotecnol Apl. 26, 24-33.

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