CKR chemokine receptors
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 7 span
Erythrocyte
T Cell
Endothelial Cell
Leukocyte
45 / 55

Expression
The nomenclature and tissue distribution of chemokine receptors is being updated. mRNA analyses suggests that these receptors are widely and differentially distributed on leukocytes.

Structure
The chemokine receptors are 7 transmembrane-spanning G protein-linked receptors.

MOLECULAR MASS
Cell Type Unreduced Reduced
46-52 kDa



Ligands
One feature of the chemokine receptors is that a number of receptors can bind several ligands and vice versa. The CCR1-CCR5 receptors bind to members of the C-C chemokine family, such as RANTES CCR1, CCR3, CCR4 and CCR5, such as MIP-1a CCR1, CCR4 and CCR5 and as MCP-1 CCR2. The CXCR1-CXCR4 receptors bind to members of the C-X-C chemokine family, either specifically such as IL-8 binding to CXCR1 CDw128a and SDF-1 binding to CXCR4 LESTR/fusin, or in a shared manner such as CXCR3 binding to both IP10 and Mig.  These interactions are usually of a high affinity, but are often within a range of affinities such as MIP-1a binds to CCR5 with a kDa = 5 nM whereas RANTES binds to CCR5 with a kDa = 470 nM.  The chemokine receptors are coupled to heterotrimeric G proteins which are believed to be of the Gia class located at the cytoplasmic face of the cell membrane.

Function
Chemokine-chemokine receptor interactions play an important role in the chemotactic recruitment of leukocytes to sites of infection and tissue damage. The signaling process involves G protein activation, leading to the generation of inositol trisphosphate with subsequent release of intracellular Ca2+, opening of Ca2+ channels and activation of protein kinase C.  Several chemokine receptors can function as co-factors in concert with CD4 for HIV-1 infection of CD4+ T cells and macrophages. CXCR4 LESTR/fusin acts as a co-factor for fusion and entry of T cell line-tropic strains of HIV-1, whereas CCR5 and, for some HIV-1 strains, CCR3 act as co-factors for macrophage-tropic isolates of HIV-1.  Dual-tropic strains of HIV-1 may utilize CXCR4, CCR5 or CCR2 as co-factors for infection of target cells.

Comments
Nomenclature: The C-C chemokines, b chemokine family, share a group of 5 known receptors designated CCR-1-CCR5.  The C-X-C chemokines, a chemokine family bind to the 4 receptors designated CXCR1-CXCR4.  In addition, the Duffy antigen on erythrocytes acts as a receptor for a wide range of C-C and C-X-C chemokines.  There are examples of viral gene products, such as US28, cytomegalovirus, and ECRF3, herpes saimiri virus, which have been shown to bind chemokines.  The Duffy antigen functions as a receptor for the malarial parasite Plasmodium vivax.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
Antibodies
2A3   View Reactivity

Revised June 25, 2008


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