Molecular cloning, functional expression, and signaling characteristics of a C-C chemokine receptor

Cell. 1993 Feb 12;72(3):415-25. doi: 10.1016/0092-8674(93)90118-a.

Abstract

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.

MeSH terms

  • Amino Acid Sequence
  • Binding, Competitive
  • Calcium / physiology
  • Cells, Cultured
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Cloning, Molecular
  • Cytokines / physiology*
  • Cytomegalovirus / metabolism
  • DNA / genetics
  • Genes, Viral
  • Humans
  • In Vitro Techniques
  • Lymphokines / physiology*
  • Macrophage Inflammatory Proteins
  • Molecular Sequence Data
  • Monokines / physiology*
  • Oligopeptides / chemistry
  • Open Reading Frames
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / physiology
  • Sequence Alignment
  • Signal Transduction
  • Viral Proteins / metabolism
  • Viral Structural Proteins / genetics

Substances

  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Cytokines
  • Lymphokines
  • Macrophage Inflammatory Proteins
  • Monokines
  • Oligopeptides
  • Receptors, Cell Surface
  • Viral Proteins
  • Viral Structural Proteins
  • DNA
  • Calcium

Associated data

  • GENBANK/L09230
  • GENBANK/L20501
  • GENBANK/L33702
  • GENBANK/L33703
  • GENBANK/L33704
  • GENBANK/L33705
  • GENBANK/L33706
  • GENBANK/L33707
  • GENBANK/L33708
  • GENBANK/L33709
  • GENBANK/M99293
  • GENBANK/X17403