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GPR39

an Orphan G-Protein-Coupled Receptor

Cloning and characterization of two 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) from human pituitary gland and brain identified a third G protein-coupled receptor (GPC-R) involved in the control of growth hormone release. The nucleotide sequence of the GHS-R is most closely related to the neurotensin receptor-1 (NT-R1) (35% overall protein identity). Two human GPC-Rs related to both the type 1a GHS-R and NT-Rs were cloned and characterized. Hybridization at low posthybridizational stringency with restriction enzyme-digested human genomic DNA resulted in the identification 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 gene (GPR39). GPR38 and GPR39 share significant amino acid sequence identity 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 structurally 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 in brain and other peripheral tissues. Fluorescence in situ hybridization localized the genes for GPR38 and GPR39 to separate chromosomes, distinct from the gene encoding the GHS-R and NT-R type 1. The ligand-binding and functional properties of GPR38 and GPR39 remain to be determined.

McKee K. K. ,et al. Genomics. 1997 Dec 15;46(3):426-34.

GPR39 signaling is stimulated by zinc ions but not by obestatin

GPR39 is an orphan member of the ghrelin receptor family that recently was suggested to be the receptor for obestatin, a peptide derived from the ghrelin precursor. Here, we compare the effect of obestatin to the effect of Zn(2+) on signal transduction and study the effect of obestatin on food intake. Although Zn(2+) stimulated inositol phosphate turnover, cAMP production, arrestin mobilization, as well as cAMP response element-dependent and serum response element-dependent transcriptional activity in GPR39-expressing cells as opposed to mock-transfected cells, no reproducible effect was obtained with obestatin in the GPR39-expressing cells. Moreover, no specific binding of obestatin could be detected in two different types of GPR39-expressing cells using three different radioiodinated forms of obestatin. By quantitative PCR analysis, GPR39 expression was readily detected in peripheral organs such as duodenum and kidney but not in the pituitary and hypothalamus, i.e. presumed central target organs for obestatin. Obestatin had no significant and reproducible effect on acute food intake in either freely fed or fasted lean mice. It is concluded that GPR39 is probably not the obestatin receptor. In contrast, the potency and efficacy of Zn(2+) in respect of activating signaling indicates that this metal ion could be a physiologically relevant agonist or modulator of GPR39.

Holst B, et al. Endocrinology. 2007 Jan;148(1):13-20. Epub 2006 Sep 7.

Expression of GPR39 in human tissues. Transcripts for GPR39 were detected by probing four Northern blots with a 32P labeled DNA fragment encompassing the complete open reading frame for GPR39. The blots were washed at high posthybridizational stringency (0.11 SSC, 65oC) and exposed to X-ray film for 3 days at -80oC. (A) Lanes 1–8: pancreas, adrenal medulla, thyroid, adrenal cortex, testis, thymus, small intestine, and stomach. (B) Lanes 1–8: spleen, thymus, prostate, testis, ovary, small intestine, colon, and leukocytes. (C) Lanes 1-8: amydala, caudate nucleus, corpus callosum, hippocampus, whole brain, substantia nigra, and thalamus. (D) Lanes 1–7: cerebellum, cerebral cortex, medulla, spinal cord, occiptal pole, frontal lobe, and temporal lobe.

McKee K.K., et al. GENOMICS 46, 426–434 (1997)

Mapping in Brain Tissue by
GPR 30 (1-23) - Antibody (H-002-83)

 

Western Blot Results

%002-85%


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