CD182 IL8RB(interleukin 8 receptor β), CXCR2 (chemokine [C-X-C motif] receptor 2) (* See available information under CD CKR), CDw128b, CD128b
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 7 span
Neutrophil
Basophil
T Cell
Leukemia cell
Epithelia
Nervous system
58 / 58
67 / 67

Expression
CD182, formally CDw128b, is expressed on neutrophils, basophils, a subset of T cells and at lower levels on monocytes and NK cells.  CD182 is expressed widely outside the hematopoietic system including the nervous system and various epithelia.  Expression is in myeloid but not in lymphocytic leukemias.

Structure
MOLECULAR FAMILY NAME: Belongs to the chemokine receptor family.

CD182 is a multi-pass type-3, 7 span 355 aa glycoprotein.  It contains an extracellular domain which contains 2 N-glycosylation sites, 7 transmembrane-spanning domain and a cytoplasmic carboxyl domain.  CD182 is shared by several receptor families.  The chemokine receptors form a division of the leukocyte chemoattractant subfamily which is part of the rhodopsin family of GPCRs.  The two IL-8 receptors,CD182 and CD181 has a 77% identity with most differences in the amino-terminal tail and the second loop as well as the intracellular C-terminal.  The differences in the extracellular region may explain the differences in ligand specificity, whereas the intracellular differences suggest there may be differences in signaling mechanisms.  The molecule contains potential Ser and Thr phosphorylation sites near the C-terminus.  CD182 is a chemokine receptor which are G-protein coupled receptor.  CD182 a high affinity receptor for IL-8.  Mice have a single IL-8 receptor which is homologous with CD182.

MOLECULAR MASS
Cell Type Unreduced Reduced
58-67 Kda

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD182 is phosphorylated upon ligand binding which is required for desensitization.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD182

CD182 binds IL-8R with a lower affinity than CD181. It also functions as the receptor for 3 other IL-8R-related CXC chemokines like melanoma, growth-stimulating activity (MSGA/GRO), neutrophil-activating peptide 2 (NAP-2) and ENA-78.  It binds to GRO-α, β, γ and NAP-2.

Function
CD182 binds to IL-8 and to GRO/MGSA and NAP-2 with a high affinity and its functions reflect a chemotactic pro-inflammatory factor.  CD182 binds other chemokines in addition to IL-8 so it may be expected to have a wider range of functions than CD181 which is specific for IL-8.  Ligation of CD182 triggers a signal cascade that leads to upregulation of adhesion molecules on the receptor-bearing cells and directed migration of the cells.  The migration, up a chemokine gradient, is generally toward sites of inflammation, the site of production of the chemokine.  CD182 is research regent in studies of inflammation and as a potential marker of functional subsets of neutrophils.  The end result of migration of neutrophils into sites of inflammation is to increase the level of inflammation.  Knockout mice have high concentration of neutrophils in the marrow and blood, a defect that is absent under germ-free conditions.  Knockout studies in mice suggested that CD182 controls positioning of oligodendrocyte precusors in developing spinal cord arresting their migration. Binding of IL-8R induces chemotaxis of neutrophils, basophils and T lymphocytes.  It activates neutrophils and basophils and increases neutrophils and monocyte adhesion to endothelial cells.  This response is mediated via a G-protein that activate a phosphatidylinositol-calcium second messenger system.  IL-8R binding to CD182 induces a transient increase in intracellular calcium levels.  The activation of phospholipase D and the respiratory burst of neutrophils in response to IL-8R can be blocked with an antibody specific for CD181, but not with an anti-CD182 antibody.  CD182 is involved with neoangiogenesis and hematopoiesis.  

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD182 IN INTACT ANIMAL: No information.


Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD182: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD182: No information.

ADDITIONAL INSIGHTS

For further information see Sprenger, H. et al (1994) J. Biol. Chem. 269: 11065-11072. 



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3579P25025
MouseA53677P35343L13239
RabbitA53752P35344L24445
RatS40296P35407X77797
Antibodies

Revised June 25, 2008


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