Cloning of complementary DNA encoding a functional human interleukin-8 receptor.
Interleukin-8 (IL-8) is an inflammatory cytokine that activates neutrophil chemotaxis, degranulation, and the respiratory burst. Neutrophils express receptors for IL-8 that are coupled to guanine nucleotide-binding proteins (G proteins); binding of IL-8 to its receptor induces the mobilization of intracellular calcium stores. A cDNA clone from HL-60 neutrophils, designated p2, has now been isolated that encodes a human IL-8 receptor. When p2 is expressed in oocytes from Xenopus laevis, the oocytes bind 125I-labeled IL-8 specifically and respond to IL-8 by mobilizing calcium stores with an EC50 of 20 nM. This IL-8 receptor has 77% amino acid identity with a second human neutrophil receptor isotype that binds IL-8 with higher affinity. It also exhibits 69% amino acid identity with a protein reported to be an N-formyl peptide receptor from rabbit neutrophils, but less than 30% identity with all other known G protein-coupled receptors, including the human N-formyl peptide receptor.
Murphy
P M
PM
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Tiffany
H L
HL
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D003001:Cloning, Molecular / Q000379:methods; D004247:DNA / Q000235:genetics; D015723:Gene Library; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D014176:Protein Biosynthesis; D011817:Rabbits; D011971:Receptors, Immunologic / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D014158:Transcription, Genetic; D014981:Xenopus
D016209:Interleukin-8; D011971:Receptors, Immunologic; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins; D004247:DNA