Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lipid transport protein, apolipoprotein E (apoE), is expressed in many peripheral tissues in vivo including the adrenal gland and testes. To investigate the role of apoE in adrenal cholesterol homeostasis, we have expressed a human apoE genomic clone in the Y1 mouse adrenocortical cell line. Y1 cells do not express endogenous apoE mRNA or protein. Expression of apoE in Y1 cells resulted in a dramatic decrease in basal steroidogenesis; secretion of fluorogenic steroid was reduced 7- to greater than 100-fold relative to Y1 parent cells. Addition of 5-cholesten-3 beta,25-diol failed to overcome the suppression of steroidogenesis in these cells. Cholesterol esterification under basal conditions, as measured by the production of cholesteryl [14C]oleate, was similar in the Y1 parent and the apoE-transfected cell lines. Upon incubation with adrenocorticotropin or dibutyryl cAMP, production of cholesteryl [14C]oleate decreased 5-fold in the Y1 parent cells but was unchanged in the apoE-transfected cell lines. These results suggest that apoE may be an important modulator of cholesterol utilization and steroidogenesis in adrenal cells.
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PMID:Expression of the human apolipoprotein E gene suppresses steroidogenesis in mouse Y1 adrenal cells. 184 1

A new member of the G protein-coupled receptor superfamily has been isolated from an ovine genomic library with a probe generated by the application of the PCR technique, using cDNA synthesized on a mRNA template isolated from the ovine pars tuberalis. This genomic clone encodes a novel receptor of 325 amino acids with seven transmembrane domains. These domains share homology with other members of this family, but the best homology is with the recently cloned human MC-1 (50% in the transmembrane domains) and MC-3 (69% in the transmembrane domains) MSH receptors and the human ACTH (42% in the transmembrane domains) receptor. When this receptor was expressed in Cos7 cells, it was able to bind a potent analogue of alpha-MSH, [Nle4,D-Phe7]-alpha-MSH (NDP-MSH), with high affinity. This binding could be displaced by pro-opiomelanocortin-derived and related peptides, with the order of potency NDP-MSH > alpha-MSH = ACTH > beta-MSH and with no effect of gamma-MSH, delta-MSH or beta-endorphin. The expressed receptor was demonstrated to be functionally coupled to the adenylate cyclase second messenger pathway, with alpha-MSH, beta-MSH and ACTH stimulating cyclic AMP production. The amount of the mRNA for this receptor was found to be very low. The tissue distribution of this receptor could only be observed using the reverse transcription-PCR technique and the receptor was found to be present in a number of somatic tissues. These data indicate that this is a new and distinct member of the melanocortin receptor family.
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PMID:Cloning and expression of a new member of the melanocyte-stimulating hormone receptor family. 806 Apr 85

A mouse genomic clone named HGMP01B has been isolated by homology screening with a probe representing part of the human melanocortin 3 receptor gene. HGMP01B was found to encode a 325 amino acid protein with all the landmarks of G-protein-coupled receptors and belonging to the growing melanocortin receptor family. This receptor displays four potential sites for N-linked glycosylation and five potential sites of phosphorylation by protein kinase C. The HGMP01B gene was found to be expressed in many tissues, including skin, adrenal gland, skeletal muscle, bone marrow, spleen, thymus, gonads, uterus, and brain. A stable Chinese hamster ovary (CHO) cell line expressing approximately 10,000 receptors per cell was established. This cell line displayed a saturable binding capacity for the radioiodinated alpha-melanocyte-stimulating hormone (alpha-MSH) analog [Nle4,D-Phe7]-alpha-MSH (NDP-MSH) with an apparent Kd of 1.47 +/- 0.15 nM. Binding of the labeled ligand was competed for by all melanocortin peptides, except beta-endorphin or corticotropin-like intermediate lobe peptide (CLIP). NDP-MSH was the most powerful competitor, followed by alpha-MSH, adrenocorticotropic hormone (ACTH), beta-MSH, the gamma-MSHs, and ACTH 4-10. Functional assays confirmed that HGMP01B, like other melanocortin receptors, stimulated adenylyl cyclase. The potency order obtained in these cyclic adenosine monophosphate (cAMP) accumulation assays was consistent with that of the binding studies. HGMP01B therefore appears as a fifth melanocortin receptor (MC5), responding mainly to alpha-MSH (EC50 = 1.07 +/- 0.13 nM) and endowed with a pharmacological profile similar to that of the melanocyte MSH (MC1) receptor, but characterized by a broad tissue distribution.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular cloning of a mouse melanocortin 5 receptor gene widely expressed in peripheral tissues. 816 9

A human genomic clone designated MC-2 is isolated. The cloned DNA codes for a protein of 325 amino acids which possesses seven hydrophobic segments, a characteristic of G-protein coupled receptors. The MC-2 receptor is expressed in brain tissue but not in the melanoma cells. When the MC-2 DNA is expressed in COS-7 cells, it binds [125I]-labelled [Nle4, D-Phe7]- alpha melanocyte stimulating hormone (NDP-MSH) which then could be displaced by melanotropic peptides alpha-MSH, beta-MSH, gamma-MSH and adrenocorticotropic hormone, but not by non-melanotropic peptide beta-endorphin. The highest affinity of 5.18 nM was for the NDP-MSH peptide. The novel MC-2 receptor and the MC-1 receptor, described earlier by us (8) showed identical order of affinity for the melanocortin peptides, but the affinities and the fold differences in the affinities to the melanocortin peptides were different when compared to the earlier described MC-1 receptor. The results suggest that the MC-2 DNA codes for a novel melanocortin receptor.
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PMID:Molecular cloning of a novel human melanocortin receptor. 856 9