CLONING AND CHARACTERIZATION OF 2 HUMAN G-PROTEIN-COUPLED RECEPTOR GENES (GPR38 AND GPR39) RELATED TO THE GROWTH-HORMONE SECRETAGOGUE AND NEUROTENSIN RECEPTORS

The recent cloning of a growth hormone secretagogue receptor (GHS-R) f rom human pituitary gland and brain identified a third G protein-coupl ed receptor (GPC-R) involved in the control of growth hormone release. The nucleotide sequence of the GHS-R is most closely related to the n eurotensin receptor-1 (NT-R1) (35% overall protein identity). Two huma n GPC-Rs related to both the type 1a GHS-R and NT-Rs were cloned and c haracterized. Hybridization at low posthybridizational stringency with restriction enzyme-digested human genomic DNA resulted in the identif ication of a genomic clone encoding a first GHS-R/NT-R family member ( GPR38). A cDNA clone was identified encoding a second GHS-R-related ge ne (GPR39). GPR38 and GPR39 share significant amino acid sequence iden tity with the GHS-R and NT-Rs 1 and 2. An acidic residue (E124) in TM- 3, essential for the binding and activation of the GHS-R by structural ly dissimilar GHSs, was conserved in GPR38 and GPR39. GPR38 is encoded by a single gene expressed in thyroid gland, stomach, and bone marrow . GPR39 is encoded by a highly conserved single-copy gene, expressed i n brain and other peripheral tissues. Fluorescence in situ hybridizati on localized the genes for GPR38 and GPR39 to separate chromosomes, di stinct from the gene encoding the GHS-R and NT-R type 1. The ligand-bi nding and functional properties of GPR38 and GPR39 remain to be determ ined. (C) 1997 Academic Press.