Family

CXC chemokine receptor 2 (IPR000057)

Short name: Chemokine_CXCR2

Family relationships

Description

Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role [PMID: 11544102]. They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system [PMID: 9689100], and endothelial cells, where they may act as either angiogenic or angiostatic factors [PMID: 7592998].

The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).

Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors [PMID: 10714678]. Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells [PMID: 10601351, PMID: 9500790]. Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).

The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.

CXCR1 and CXCR2, also known as interleukin 8 receptor alpha and beta, respectively [PMID: 8384312], are closely-related receptors. They act as specific receptors for the CXCL8 and CXCL6 chemokines, which have a glutamate-leucine-arginine (ELR) motif in their N-terminal domains [PMID: 16720046]. CXCR2 also binds additional ELR motif-containing CXC chemokines (such as CXCL1, CXCL2, CXCL3, CXCL5 and CXCL7) with high affinity [PMID: 16720046].

CXCR1 and CXCR2 are expressed on all granulocytes, monocytes, and mast cells and on some CD8+ T-cells and CD56+ natural killer (NK) cells [PMID: 7527448]. Equal amounts of CXCR1 and CXCR2 are present on neutrophils [PMID: 10878382, PMID: 8955112, PMID: 12239185, PMID: 15967374, PMID: 1379593], but it appears that monocytes and positive lymphocytes express more CXCR2 than CXCR1 [PMID: 7527448].

This entry represents CXCR2. The angiogenic effects of CXCL8 in intestinal microvascular endothelial cells are mediated by this receptor [PMID: 12496258]. It has been suggested that the receptor may be a potential theraputic target in acute lung injury [PMID: 22719179].

GO terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway
GO:0006935 chemotaxis

Molecular Function

GO:0016494 C-X-C chemokine receptor activity
GO:0019959 interleukin-8 binding

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PRINTS