MOLECULAR-CLONING, CHARACTERIZATION, AND LOCALIZATION OF THE HUMAN HOMOLOG TO THE REPORTED BOVINE NPY Y3-RECEPTOR - LACK OF NPY BINDING ANDACTIVATION

A cDNA clone encoding the human homolog of the bovine cDNA clone LCR1 was isolated from a human lung cDNA library. The 1,670-bp-long nucleot ide sequence predicts a single open reading frame of 352 amino acids, with a 92% amino acid identity to a bovine sequence reported to repres ent the neuropeptide Y (NPY) Y3 receptor. The amino acid sequence shar es features common to many other G-protein-coupled receptors, includin g the seven transmembrane regions and putative glycosylation and phosp horylation sites. Polymerase chain reaction (PCR) analysis of human-ha mster hybrid cell DNA reveals that the corresponding gene is located o n human chromosome 2. Although the ligand for the bovine receptor has previously been identified as NPY in binding studies, extensive analys is with the human homolog transfected in several different cell lines failed to confirm this classification. Furthermore, the receptor shows 36% identity to both the human interleukin-8 (IL-8) and angiotensin I I receptors but only 21% identity to the human NPY Y1 receptor. In add ition, NPY and a number of other ligands fail to induce any change in cytosolic calcium levels in transfected cells, suggesting that this cl one represents a novel neuropeptide receptor.