PARATHYROID-HORMONE PARATHYROID-HORMONE RELATED PEPTIDE RECEPTOR GENE TRANSCRIPTS ARE EXPRESSED FROM TISSUE-SPECIFIC AND UBIQUITOUS PROMOTERS

被引:65
作者
MCCUAIG, KA [1 ]
LEE, HS [1 ]
CLARKE, JC [1 ]
ASSAR, H [1 ]
HORSFORD, J [1 ]
WHITE, JH [1 ]
机构
[1] MCGILL UNIV,DEPT PHYSIOL,MONTREAL,PQ H3G 1Y6,CANADA
基金
英国医学研究理事会;
关键词
D O I
10.1093/nar/23.11.1948
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Parathyroid hormone (PTH) and PTH related peptide (PTHrP) stimulate diverse physiological responses in a number of tissues by binding to the same receptor, We have previously cloned the gene encoding the mouse PTH/PTHrP receptor (PTHR), and have identified a promoter region, The first exon transcribed from this promoter contains untranslated sequence and is followed by an exon encoding signal sequence and the first amino acids of the mature polypeptide, We have now identified and characterized a second promoter region, located >3 kb upstream of the original, Four partial cDNA clones, amplified from mouse kidney RNA by reverse transcription followed by the polymerase chain reaction, contain sequence corresponding to two previously unidentified exons composed of untranslated sequence, The second (3') of the two exons is spliced to the previously identified signal sequence exon, These cDNAs are highly homologous to the 5' end of a cDNA isolated from human kidney, strongly suggesting that the promoter region is conserved between mouse and humans, RNase protection and primer extension experiments have identified several transcriptional start sites extending over a region of -100 bp, Unlike the previously identified promoter, this promoter is not (G+C)-rich. It lacks a consensus TATA element, but does contain a consensus CCAAT box, We have determined the expression patterns of both promoters by RNase protection with total and poly A(+) RNA from several mouse tissues. The newly identified promoter is highly tissue specific, being strongly active in kidney and weakly active in liver, but not expressed in the other tissues studied, The previously identified (G+C)-rich promoter is expressed in all tissues studied, This indicates that the PTHR gene expression is controlled by regulatory signals specific to kidney and liver, as well as signals functioning in a wide variety of cell types, These results may provide insight into certain defects in PTH signalling found in humans.
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页码:1948 / 1955
页数:8
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