Molecular cloning of a novel G protein-coupled receptor related to the opiate receptor family.
A cDNA clone encoding a novel G protein-linked receptor was isolated from a rat cerebral cortex cDNA library using a polymerase chain reaction-amplified cDNA fragment as a probe. This 2.4-kb clone encodes a 367 amino acid protein with seven putative transmembrane spanning domains. The protein is highly homologous to the cloned micro, delta, and kappa opioid receptors and shares with them structural features such as three glycosylation sites in the amino terminus, a cyclic AMP-dependent kinase phosphorylation site in the third cytoplasmic loop, an aspartic acid residue in the second transmembrane domain, and a palmitoylation site on the intracellular carboxy terminus. The receptor is also homologous with members of the somatostatin receptor family, yet it binds neither opiate nor somatostatin ligands. Northern blot analysis reveals two transcripts of 3.2 and 7.6 kb that are predominantly expressed in the cerebral cortex and hypothalamus. In situ hybridization analysis also shows a high abundance of mRNA in the cerebral cortex, hippocampus, amygdala, hypothalamus, thalamus, and dorsal raphe nuclei. It is suggested that the endogenous ligand for this receptor may represent a novel neuropeptide that may be closely related to the opiate peptide family.
Lachowicz
J E
JE
Molecular Neuropharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Shen
Y
Y
Monsma
F J
FJ
Sibley
D R
DR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001923:Brain Chemistry; D016466:CHO Cells; D002460:Cell Line; D002540:Cerebral Cortex / Q000737:chemistry / Q000648:ultrastructure; D003001:Cloning, Molecular; D006224:Cricetinae; D004247:DNA / Q000032:analysis* / Q000235:genetics; D019204:GTP-Binding Proteins / Q000032:analysis / Q000235:genetics*; D006624:Hippocampus / Q000737:chemistry / Q000648:ultrastructure; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics*; D011957:Receptors, Opioid / Q000032:analysis / Q000235:genetics*; D017465:Receptors, Opioid, delta / Q000032:analysis / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000032:analysis / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000032:analysis / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
C091041:G protein-coupled receptor C3; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004247:DNA; D019204:GTP-Binding Proteins