Linked Life Data

8386612

Source:http://linkedlifedata.com/resource/pubmed/id/8386612

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1993-5-25
pubmed:databankReference
pubmed:abstractText
Identical complementary DNAs (cDNAs) that encode a 593-amino acid human PTH (PTH)/PTH-related peptide (PTHrP) receptor were isolated by hybridization techniques from two cDNA libraries which had been constructed from human kidney and human osteoblast-like osteosarcoma cells (SaOS-2). Northern blot analysis of total RNA from human bone- and kidney-derived tissue revealed one single major messenger RNA species of about 2.5 kilobases in both tissues. The human PTH/PTHrP receptor has 91% and 81% identity, respectively, with the previously cloned rat and opossum receptors, indicating a high degree of conservation among mammals. Despite this striking degree of amino-acid conservation, the human PTH/PTHrP receptor has several unique biological properties when transiently expressed in COS-7 cells. The apparent dissociation constants for [Nle8,18,Tyr34] bovine PTH(1-34) amide [bPTH(1-34)] are similar for the human and the rat receptor (approximately 8 vs. approximately 15 nM) whereas [Tyr36]PTHrP(1-36) amide has a slightly lower affinity for the human (15-40 nM) than for the rat receptor (approximately 15 nM). Both ligands stimulate efficiently and with similar efficacy the accumulation of intracellular cAMP. The affinities for the antagonists [Nle8,18,Tyr34] bPTH(3.34) amide [bPTH(3-34)] and in particular for [Nle8,18,Tyr34] bPTH(7-34) amide [bPTH(7-34)] are considerably higher for the human receptor, e.g. approximately 8 nM vs. 30 nM for bPTH(3-34) and approximately 100 nM vs. 5000 nM for bPTH(7-34), respectively. Similar biological findings were previously attributed to differences in species- and/or organ-specific PTH/PTHrP receptors. The expression of the recombinant, highly homologous rat and human receptors in a uniform environment indicate that the moderate differences in the primary receptor structure have profound consequences for the receptor binding affinity of amino-terminally truncated PTH analogs. Furthermore, the molecular cloning of identical cDNAs encoding a human PTH/PTHrP receptor from the two major target organs for PTH, bone and kidney, provides strong evidence for one single PTH/PTHrP receptor in both organs, although additional and/or alternatively spliced receptors cannot be excluded.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
132
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2157-65
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8386612-Amino Acid Sequence, pubmed-meshheading:8386612-Animals, pubmed-meshheading:8386612-Base Sequence, pubmed-meshheading:8386612-Blotting, Northern, pubmed-meshheading:8386612-Bone and Bones, pubmed-meshheading:8386612-Cloning, Molecular, pubmed-meshheading:8386612-DNA, pubmed-meshheading:8386612-Glycosylation, pubmed-meshheading:8386612-Kidney, pubmed-meshheading:8386612-Molecular Sequence Data, pubmed-meshheading:8386612-Osteosarcoma, pubmed-meshheading:8386612-Polymerase Chain Reaction, pubmed-meshheading:8386612-Rats, pubmed-meshheading:8386612-Receptor, Parathyroid Hormone, Type 1, pubmed-meshheading:8386612-Receptors, Cell Surface, pubmed-meshheading:8386612-Receptors, Parathyroid Hormone, pubmed-meshheading:8386612-Sequence Homology, Amino Acid, pubmed-meshheading:8386612-Tumor Cells, Cultured
pubmed:year
1993
pubmed:articleTitle
Identical complementary deoxyribonucleic acids encode a human renal and bone parathyroid hormone (PTH)/PTH-related peptide receptor.
pubmed:affiliation
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't