Source:http://linkedlifedata.com/resource/pubmed/id/11137300
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-2
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| pubmed:dateCreated |
2001-1-23
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| pubmed:abstractText |
PTP-1B is a ubiquitously expressed intracellular protein tyrosine phosphatase (PTP) that has been implicated in the negative regulation of insulin signaling. Mice deficient in PTP-1B were found to have an enhanced insulin sensitivity and a resistance to diet-induced obesity. Interestingly, the human PTP-1B gene maps to chromosome 20q13.1 in a region that has been associated with diabetes and obesity. Although there has been a partial characterization of the 3' end of the human PTP-1B gene, the complete gene organization has not been described. In order to further characterize the PTP-1B gene, we have cloned and determined the genomic organization for both the human and mouse PTP-1B genes including the promoter. The human gene spans >74 kb and features a large first intron of >54 kb; the mouse gene likewise contains a large first intron, although the exact size has not been determined. The organization of the human and mouse PTP-1B genes is identical except for an additional exon at the 3' end of the human that is absent in the mouse. The mouse PTP-1B gene maps to the distal arm of mouse chromosome 2 in the region H2-H3. This region is associated with a mouse obesity quantitative trait locus (QTL) and is syntenic with human chromosome 20. The promoter region of both the human and mouse genes contain no TATA box but multiple GC-rich sequences that contain a number of consensus SP-1 binding sites. The basal activity of the human PTP-1B promoter was characterized in Hep G2 cells using up to 8 kb of 5' flanking sequence. A 432 bp promoter construct immediately upstream of the ATG was able to confer maximal promoter activity. Within this sequence, there are at least three GC-rich sequences and one CCAAT box, and deletion of any of these elements results in decreased promoter activity. In addition, the promoter in a number of mouse strains contains, 3.5 kb upstream of the start codon, an insertion of an intracisternal a particle (IAP) element that possibly could alter the expression of PTP-1B mRNA in these strains.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkaline Phosphatase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0378-1119
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
30
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| pubmed:volume |
260
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
145-53
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:11137300-Alkaline Phosphatase,
pubmed-meshheading:11137300-Amino Acid Sequence,
pubmed-meshheading:11137300-Animals,
pubmed-meshheading:11137300-Base Sequence,
pubmed-meshheading:11137300-Chromosome Mapping,
pubmed-meshheading:11137300-Cloning, Molecular,
pubmed-meshheading:11137300-DNA,
pubmed-meshheading:11137300-Exons,
pubmed-meshheading:11137300-Gene Expression,
pubmed-meshheading:11137300-Gene Expression Regulation,
pubmed-meshheading:11137300-Genes,
pubmed-meshheading:11137300-Genes, Intracisternal A-Particle,
pubmed-meshheading:11137300-Humans,
pubmed-meshheading:11137300-In Situ Hybridization, Fluorescence,
pubmed-meshheading:11137300-Introns,
pubmed-meshheading:11137300-Male,
pubmed-meshheading:11137300-Mice,
pubmed-meshheading:11137300-Mice, Inbred Strains,
pubmed-meshheading:11137300-Molecular Sequence Data,
pubmed-meshheading:11137300-Mutagenesis, Insertional,
pubmed-meshheading:11137300-Promoter Regions, Genetic,
pubmed-meshheading:11137300-Protein Tyrosine Phosphatase, Non-Receptor Type 1,
pubmed-meshheading:11137300-Protein Tyrosine Phosphatases,
pubmed-meshheading:11137300-RNA, Messenger,
pubmed-meshheading:11137300-Recombinant Fusion Proteins,
pubmed-meshheading:11137300-Sequence Analysis, DNA,
pubmed-meshheading:11137300-Sequence Homology, Nucleic Acid,
pubmed-meshheading:11137300-Tissue Distribution,
pubmed-meshheading:11137300-Tumor Cells, Cultured
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| pubmed:year |
2000
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| pubmed:articleTitle |
Genomic characterization of the human and mouse protein tyrosine phosphatase-1B genes.
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| pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Merck Frosst Center for Therapeutic Research, Kirkland, Quebec H9H 3L1, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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