Interleukin−8 (IL−8) is the prototype for a family of at least eight neutrophil chemoattractants whose genes map to human chromosome 4q13−q21. Two human IL−8 receptors, IL8RA and IL8RB, are known from cDNA cloning; IL8RA is a promiscuous receptor for at least two other related ligands, GROalpha and NAP−2. We now report cloning of the genes for IL8RA, IL8RB and a recently inactivated pseudogene of receptor A (IL8RAP). These form a cluster of only three genes in the superfamily of G protein−coupled receptors (GPCRs) and map to 2q34−q35. The revolutionary diversity displayed by the IL−8 ligand−receptor complex — ligand promiscuity for IL−8, receptor promiscuity for IL8RA, gene duplication for both ligands and receptors and gene extinction in the case of IL8RAP — is unprecedented for the GPCR superfamily.
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