Source:http://linkedlifedata.com/resource/pubmed/id/17052199
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
Pt 5
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pubmed:dateCreated |
2006-10-20
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pubmed:abstractText |
The transcription factor PDX-1 (pancreatic duodenal homeobox-1) is required for normal pancreatic development and for the function of insulin-producing islet beta-cells in mammals. We have shown previously that glucose regulates insulin gene expression in part through the activation and translocation of PDX-1 from the nuclear periphery to the nucleoplasm. We have also found that PASK [PAS (Per-Arnt-Sim) kinase], a member of the nutrient-regulated family of protein kinases, is activated in response to glucose challenge in beta-cells and is involved in the regulation of expression of PDX-1. Purified PASK efficiently phosphorylated recombinant PDX-1 in vitro on a single site (Thr-152). To determine the impact of phosphorylation at this site, we generated wild-type and mutant (T152A, T152D and T152E) forms of PDX-1 and examined the distribution of each of these in clonal MIN6 beta-cells by immunocytochemical analysis. Unexpectedly, only the T152D mutation significantly affected subcellular distribution, increasing the ratio of nuclear/cytosolic labelling at low and high glucose concentrations, suggesting that phosphorylation at Thr-152 inhibits nuclear uptake in response to glucose. Based on these results, experiments to examine the contribution of Thr-152 to the overall phosphorylation of PDX-1 in intact cells will be undertaken.
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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/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PAS domain kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/pancreatic and duodenal homeobox 1...
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0300-5127
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
791-3
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pubmed:dateRevised |
2011-6-1
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pubmed:meshHeading |
pubmed-meshheading:17052199-Cell Nucleus,
pubmed-meshheading:17052199-Duodenum,
pubmed-meshheading:17052199-Homeodomain Proteins,
pubmed-meshheading:17052199-Homeostasis,
pubmed-meshheading:17052199-Humans,
pubmed-meshheading:17052199-Insulin-Secreting Cells,
pubmed-meshheading:17052199-Mutation,
pubmed-meshheading:17052199-Pancreas,
pubmed-meshheading:17052199-Protein Transport,
pubmed-meshheading:17052199-Protein-Serine-Threonine Kinases,
pubmed-meshheading:17052199-Trans-Activators
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pubmed:year |
2006
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pubmed:articleTitle |
Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal homeobox-1 nuclear import in pancreatic beta-cells.
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pubmed:affiliation |
Henry Wellcome Signalling Laboratories and Department of Biochemistry, University of Bristol, Bristol BS8 ITD, UK.
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pubmed:publicationType |
Journal Article
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