Source:http://linkedlifedata.com/resource/pubmed/id/17965023
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
52
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| pubmed:dateCreated |
2007-12-24
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| pubmed:abstractText |
It is well known that insulin receptor substrates (IRS) act as a mediator for signal transduction of insulin, insulin-like growth factors, and several cytokines. To identify proteins that interact with IRS and modulate IRS-mediated signals, we performed yeast two-hybrid screening with IRS-1 as bait. Out of 109 cDNA-positive clones identified from a human placental cDNA library, two clones encoded 53BP2, p53-binding protein 2 (53BP2S), a short form splicing variant of the apoptosis-stimulating protein of p53 that possesses Src homology region 3 domain, and ankyrin repeats domain, and had been reported to interact with p53, Bcl-2, and NF-kappaB. Interaction of 53BP2S with IRS-1 was confirmed by glutathione S-transferase pull-down and co-immunoprecipitation assays in COS-7 cells and 3T3-L1 adipocytes. The Src homology region 3 domain and ankyrin repeats domain of 53BP2S were responsible for its interaction with IRS-1, whereas the phosphotyrosine binding domain and a central domain (amino acid residues 750-861) of IRS-1 were required for its interaction with 53BP2S. In CHO-C400 cells, expression of 53BP2S reduced insulin-stimulated IRS-1 tyrosine phosphorylation with a concomitant enhancement of IRS-2 tyrosine phosphorylation. In addition, the amount of the phosphatidylinositol 3-kinase regulatory p85 subunit associated with tyrosine-phosphorylated proteins, and activation of Akt was enhanced by 53BP2S expression. Although 53BP2S also enhanced Akt activation in 3T3-L1 adipocytes, insulin-induced glucose transporter 4 translocation was markedly inhibited in accordance with reduction of insulin-induced AS160 phosphorylation. Together these data demonstrate that 53BP2S interacts and modulates the insulin signals mediated by IRSs.
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/IRS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IRS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Irs1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Irs2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
28
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| pubmed:volume |
282
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
37747-58
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:17965023-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:17965023-Alternative Splicing,
pubmed-meshheading:17965023-Animals,
pubmed-meshheading:17965023-Apoptosis,
pubmed-meshheading:17965023-CHO Cells,
pubmed-meshheading:17965023-COS Cells,
pubmed-meshheading:17965023-Carrier Proteins,
pubmed-meshheading:17965023-Cercopithecus aethiops,
pubmed-meshheading:17965023-Cricetinae,
pubmed-meshheading:17965023-Cricetulus,
pubmed-meshheading:17965023-Insulin,
pubmed-meshheading:17965023-Insulin Receptor Substrate Proteins,
pubmed-meshheading:17965023-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:17965023-Mice,
pubmed-meshheading:17965023-Phosphoproteins,
pubmed-meshheading:17965023-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:17965023-Signal Transduction,
pubmed-meshheading:17965023-src Homology Domains
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| pubmed:year |
2007
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| pubmed:articleTitle |
53BP2S, interacting with insulin receptor substrates, modulates insulin signaling.
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| pubmed:affiliation |
Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, the University of Tokyo, Tokyo, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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