Monocyte chemotactic protein-2 (MCP-2) uses CCR1 and CCR2B as its functional receptors.
Monocyte chemotactic protein (MCP)-2 is a member of the C-C chemokine subfamily, which shares more than 60% sequence homology with MCP-1 and MCP-3 and about 30% homology with macrophage inflammatory protein (MIP)-1alpha, regulated on activation of normal T cell expressed (RANTES), and MIP-1beta. Despite this considerable sequence homology to other C-C chemokines, MCP-2 appears to have unique functional properties in comparison with other C-C chemokines such as MCP-1 and MCP-3. Although evidence obtained from studies on leukocytes suggested that MCP-2 may share the receptors with these C-C chemokines, the actual functional receptors for MCP-2 have not yet been identified. In this study, by using radioiodinated MCP-2, we identified high affinity binding sites for MCP-2 on human peripheral blood monocytes. The MCP-2 binding was competed for by MCP-1 and MCP-3, but less well by MIP-1alpha or RANTES. In experiments using cells transfected with C-C chemokine receptors, 125I-MCP-2 bound to human embryonic kidney 293 cells transfected with CCR1 or CCR2B, known to also bind MIP-1alpha/RANTES and MCP-1, respectively, but both shared by MCP-3. The binding of 125I-MCP-2 to these receptor-transfected cells was displaced completely by chemokines that bind to these receptors. Both CCR1- and CCR2B-transfected 293 cells showed significant migration in response to MCP-2, in addition to responding to other specific chemokines. These results clearly demonstrate that MCP-2, unlike MCP-1, uses both CCR1 as well as CCR2B as its functional receptors, and this accounts for the unique activities of MCP-2.
Gong
X
X
Intramural Research Support Program,SAIC-Frederick, NCI-FCRDC, Frederick, Maryland 21702, USA.
Gong
W
W
Kuhns
D B
DB
Ben-Baruch
A
A
Howard
O M
OM
Wang
J M
JM
D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism / Q000494:pharmacology; D054412:Chemokine CCL8; D018925:Chemokines / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism / Q000494:pharmacology; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism* / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
C515453:CCL8 protein, human; C515300:CCR1 protein, human; C515334:CCR2 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054412:Chemokine CCL8; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D011994:Recombinant Proteins