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| http://purl.uniprot.org/citations/20427478 | http://www.w3.org/2000/01/rdf-schema#comment | "Tuberous sclerosis complex proteins 1-2 (TSC1-TSC2) complex integrates both nutrient and hormonal signaling and is a critical negative regulator of mammalian target of rapamycin (mTOR) complex 1. The use of different beta-cell lines expressing or not the insulin receptor (IR(+/+) and IR(-/-)) or with a reconstituted expression of IR isoform A or B (Rec A and Rec B) revealed that both phosphatidylinositol 3-kinase/Akt/TSC/mTOR complex 1 and MAPK kinase/ERK pathways mediate insulin signaling in IR(+/+)-, IRA-, or IRB-expressing cells. However, glucose signaling was mediated by MAPK kinase/ERK and AMP-activated protein kinase pathways as assessed in IR(-/-) cells. The effect of insulin on Akt phosphorylation was completely inhibited by the use of the phosphatidylinositol 3-kinase inhibitor wortmannin in IR(+/+) and Rec B cells, a partial inhibitory effect being observed in Rec A cell line. The knockdown of TSC2 expression up-regulated the downstream basal phosphorylation of 70-kDa ribosomal protein S6 kinase (p70S6K) and mTOR. More importantly, upregulation of p70S6K signaling impaired insulin-stimulated phosphorylation of Akt Ser(473) and p70S6K in IR(+/+) and Rec B but not in Rec A cell lines. In fact, insulin receptor substrate-1 Ser(307) phosphorylation signal in Rec B was stronger than in Rec A cell line during insulin action. Rec A cells induced a higher proliferation rate compared with Rec B or IR(+/+) during serum stimulation. Thus, we propose that the regulation of TSC2 phosphorylation by insulin or glucose independently integrates beta-cell proliferation signaling, the relative expression of IRA or IRB isoforms in pancreatic beta cells playing a major role."xsd:string |
| http://purl.uniprot.org/citations/20427478 | http://purl.org/dc/terms/identifier | "doi:10.1210/en.2010-0048"xsd:string |
| http://purl.uniprot.org/citations/20427478 | http://purl.uniprot.org/core/author | "Benito M."xsd:string |
| http://purl.uniprot.org/citations/20427478 | http://purl.uniprot.org/core/author | "Guillen C."xsd:string |
| http://purl.uniprot.org/citations/20427478 | http://purl.uniprot.org/core/author | "Bartolome A."xsd:string |
| http://purl.uniprot.org/citations/20427478 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20427478 | http://purl.uniprot.org/core/name | "Endocrinology"xsd:string |
| http://purl.uniprot.org/citations/20427478 | http://purl.uniprot.org/core/pages | "3084-3094"xsd:string |
| http://purl.uniprot.org/citations/20427478 | http://purl.uniprot.org/core/title | "Role of the TSC1-TSC2 complex in the integration of insulin and glucose signaling involved in pancreatic beta-cell proliferation."xsd:string |
| http://purl.uniprot.org/citations/20427478 | http://purl.uniprot.org/core/volume | "151"xsd:string |
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