| pubmed-article:21098738 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21098738 | lifeskim:mentions | umls-concept:C0031715 | lld:lifeskim |
| pubmed-article:21098738 | lifeskim:mentions | umls-concept:C0036720 | lld:lifeskim |
| pubmed-article:21098738 | lifeskim:mentions | umls-concept:C0542341 | lld:lifeskim |
| pubmed-article:21098738 | lifeskim:mentions | umls-concept:C1366765 | lld:lifeskim |
| pubmed-article:21098738 | lifeskim:mentions | umls-concept:C2603343 | lld:lifeskim |
| pubmed-article:21098738 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:21098738 | pubmed:dateCreated | 2011-4-27 | lld:pubmed |
| pubmed-article:21098738 | pubmed:abstractText | The identity of specific serine phosphorylation residues of insulin receptor substrate (IRS)-2 and their impact on insulin signal transduction are largely unknown. Ser(675) and Ser(907) of mouse IRS-2 are adjacent to PI 3-kinase or Grb2 binding domains, respectively. Using monoclonal phosphosite-specific antibodies, we demonstrated the phosphorylation of both serines after stimulation of Fao hepatoma cells with insulin, anisomycin, or phorbol esters. Phosphorylation of both sites was a late and prolonged event during insulin treatment and was also detected in liver tissue of insulin-treated as well as refed mice. Inhibition and siRNA-mediated knockdown of ERK1/2 indicated that the insulin-induced phosphorylation of Ser(907) was ERK dependent. Phosphorylation of Ser(907) did not prevent the insulin-induced association of IRS-2 with Grb2, but phosphorylation of the adjacent Tyr(911) was proved to be crucial in HEK 293 cells expressing IRS-2 Ala mutants. The insulin-induced phosphorylation of Ser(675) was prevented by inhibition and siRNA-mediated knockdown of mTOR but not of p70(S6K1). Mutation of Ser(675) to Ala did not affect downstream insulin signaling but increased the half-life of the protein, suggesting an involvement of phospho-Ser(675) in an accelerated degradation of IRS-2. Moreover, the insulin-induced degradation of IRS-2 was blocked by inhibition of mTOR. We conclude that the two novel insulin-dependent serine phosphorylation sites of IRS-2 were not involved in the regulation of the adjacent PI 3-kinase and Grb2 binding domains but might be implicated in the ERK- and mTOR-mediated negative feedback control. | lld:pubmed |
| pubmed-article:21098738 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21098738 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21098738 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21098738 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21098738 | pubmed:month | May | lld:pubmed |
| pubmed-article:21098738 | pubmed:issn | 1522-1555 | lld:pubmed |
| pubmed-article:21098738 | pubmed:author | pubmed-author:HennigeAnita... | lld:pubmed |
| pubmed-article:21098738 | pubmed:author | pubmed-author:WeigertCoraC | lld:pubmed |
| pubmed-article:21098738 | pubmed:author | pubmed-author:HäringHans-Ul... | lld:pubmed |
| pubmed-article:21098738 | pubmed:author | pubmed-author:SchenkMartinM | lld:pubmed |
| pubmed-article:21098738 | pubmed:author | pubmed-author:KremmerElisab... | lld:pubmed |
| pubmed-article:21098738 | pubmed:author | pubmed-author:LehmannRainer... | lld:pubmed |
| pubmed-article:21098738 | pubmed:author | pubmed-author:SchleicherErw... | lld:pubmed |
| pubmed-article:21098738 | pubmed:author | pubmed-author:FritscheLouis... | lld:pubmed |
| pubmed-article:21098738 | pubmed:author | pubmed-author:NeukammSabine... | lld:pubmed |
| pubmed-article:21098738 | pubmed:author | pubmed-author:Hunder-GugelA... | lld:pubmed |
| pubmed-article:21098738 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21098738 | pubmed:volume | 300 | lld:pubmed |
| pubmed-article:21098738 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21098738 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21098738 | pubmed:pagination | E824-36 | lld:pubmed |
| pubmed-article:21098738 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
| pubmed-article:21098738 | pubmed:meshHeading | pubmed-meshheading:21098738... | lld:pubmed |
| pubmed-article:21098738 | pubmed:meshHeading | pubmed-meshheading:21098738... | lld:pubmed |
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| pubmed-article:21098738 | pubmed:meshHeading | pubmed-meshheading:21098738... | lld:pubmed |
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| pubmed-article:21098738 | pubmed:meshHeading | pubmed-meshheading:21098738... | lld:pubmed |
| pubmed-article:21098738 | pubmed:meshHeading | pubmed-meshheading:21098738... | lld:pubmed |
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| pubmed-article:21098738 | pubmed:meshHeading | pubmed-meshheading:21098738... | lld:pubmed |
| pubmed-article:21098738 | pubmed:year | 2011 | lld:pubmed |
| pubmed-article:21098738 | pubmed:articleTitle | Insulin-induced serine phosphorylation of IRS-2 via ERK1/2 and mTOR: studies on the function of Ser675 and Ser907. | lld:pubmed |
| pubmed-article:21098738 | pubmed:affiliation | Dept. of Internal Medicine, Div. of Pathobiochemistry and Clinical Chemistry, Univ. of Tuebingen, Otfried-Mueller-Straße 10, 72076 Tuebingen, Germany. | lld:pubmed |
| pubmed-article:21098738 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21098738 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
