CD181 IL-8RA (interleukin 8 receptor α), CXCR1 (chemokine [C-X-C motif] receptor 1) (* See available information under CD CKR), CXCR1, CD128A, CDw128a 

, CDw128a, C-C CKR-1, C-C-CKR-1
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 7 span
Neutrophil
Basophil
T Cell
Leukemia cell
58 / 58
67 / 67

Expression
CD181, formally CDw128a, is expressed on neutrophils, a subset of T cells, basophils and at lower levels on monocytes and NK cells.  Expression is in myeloid but not lymphocyte leukemias.

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

CD181 is a multi-pass type-3, 7 span 350 aa  glycoprotein.  It contains an extracellular domain which contains 2 N-glycosylation sites, 7 transmembrane-spanning domains and a cytoplasmic carboxyl terminal domain.  CD181 is shared by several receptors families.  The chemokine receptors form a division of leukocyte chemoattractant subfamily, which is part of the rhodopsin family of GPCRs.  The two IL-6 receptors, CD181 and CR182 are 77% identical and show most differences in the amino-terminal tail and second loop, as well as the intracellular C-terminal.  The differences in the extracellular region may explain 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.  CD181 is a chemokine receptor which are part of a subfamily of related G-protein coupled receptors that transduce signals for the IL-8 family of pro-inflammatory cytokines.  CD181 is a high affinity receptor for IL8α.  Mice have a single IL-8 receptor, which is most homologous with CD182.

MOLECULAR MASS
Cell Type Unreduced Reduced
58-67 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD181

CD181 binds IL-8R with a high affinity of  kDa = 3.6 nM. 

Function
CD181 is a high affinity receptor for IL-8 and its function reflect the function of a chemotactic pro-inflammatory factor.  Ligation of CD181 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.  CD181 is a research reagent in studies of inflammation and with potential as a 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 concentrations of neutrophils in the marrow and blood, a defect that is absent under germ-free conditions.  Activities of CD181 includes chemoattraction and activation of neutrophils, chemotaxis and activation of monocytes, the selective chemotaxis of memory T cells, the inhibition of hematopoietic stem cell proliferation and the induction if neutrophil infiltration in vivo.  It activates T lymphocytes, neutrophils and basophils and increases neutrophils and monocyte adhesion to endothelial cells.  IL-8R binding to CD181 induces a transient increase in intracellular calcium levels and transduces a signal through a G-protein activated second messenger system.  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.  CD181 is involved in neoangiogenesis.  Knockout studies in mice suggested that the protein, which is a receptor for IL-8, inhibits embryonic oligodendrocyte precursor migration in developing spinal cord.  The receptor binds to IL-8 with a high affinity and to MGSA/GRO with a low affinity. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD181 IN INTACT ANIMAL: No information.


Comments
The cDNA clone originally reported to encode the rabbit N-formyl peptide receptor is now identified as the rabbit orthologue of CD181 with a 79% identity.

MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD181: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD181: No information.

ADDITIONAL INSIGHTS

For further information see Holmes, W.E. et al (1991) Science 253: 1278-1280.
 


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3577P25024
RabbitA23669P21109M58021
Antibodies
6C6   View Reactivity

Revised June 25, 2008


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