Molecular cloning, functional expression, and signaling characteristics of a C-C chemokine receptor.
The immunoregulatory proteins C-C chemokines are potent chemoattractants of lymphocytes and monocytes, as well as activators and attractants of eosinophils and basophils. We have isolated a cDNA that encodes a seven transmembrane-spanning receptor, with homology to other chemoattractant receptors, that encodes a protein designated C-C CKR-1 that acts as a receptor for the C-C chemokines. Human and murine macrophage inflammatory protein 1 alpha (MIP-1 alpha), human human monocyte chemotactic protein 1 (MCP-1), and RANTES all bind to the C-C CKR-1 with varying affinities. Chemokine binding affinity does not predict how well the ligand will transmit a signal through the receptor: RANTES and human MIP-1 alpha induce a similar intracellular calcium flux while binding with disparate affinities, while MCP-1 and human MIP-1 beta induce calcium mobilization only at high concentrations. Finally, C-C chemokines were shown to bind a C-C CKR-1-related gene product encoded by cytomegalovirus, suggesting a role for C-C chemokines in viral immunity.
Neote
K
K
Department of Immunology, Genentech, Incorporated, South San Francisco, California 94080.
DiGregorio
D
D
Mak
J Y
JY
Horuk
R
R
Schall
T J
TJ
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D003001:Cloning, Molecular; D016207:Cytokines / Q000502:physiology*; D003587:Cytomegalovirus / Q000378:metabolism; D004247:DNA / Q000235:genetics; D005814:Genes, Viral; D006801:Humans; D066298:In Vitro Techniques; D008222:Lymphokines / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins; D008969:Molecular Sequence Data; D015846:Monokines / Q000502:physiology*; D009842:Oligopeptides / Q000737:chemistry; D016366:Open Reading Frames; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology; D016415:Sequence Alignment; D015398:Signal Transduction; D014764:Viral Proteins / Q000378:metabolism; D015678:Viral Structural Proteins / Q000235:genetics
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016207:Cytokines; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D014764:Viral Proteins; D015678:Viral Structural Proteins; D004247:DNA; D002118:Calcium