| http://purl.uniprot.org/citations/16362038 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16362038 | http://www.w3.org/2000/01/rdf-schema#comment | "Insulin-like growth factor-I inhibits transforming growth factor-beta (TGF-beta) signaling by blocking activation of Smad3 (S3), via a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent pathway. Here we provide the first report that the kinase activity of Akt is necessary for its ability to suppress many TGF-beta responses, including S3 activation and induction of apoptosis. Wild-type and myristoylated Akts (Akt(WT) and Akt(Myr)) suppress TGF-beta-induced phospho-activation of S3 but not Smad2 (S2), whereas kinase-dead Akt1 (Akt1K179M) or dominant-negative PI3K enhances TGF-beta-induced phospho-activation of both S2 and S3. Using siRNA, rapamycin (Rap), and adenoviral expression for FKBP12-resistant and constitutively active TGF-beta type I receptor (ALK5), we demonstrate that mammalian target of Rap (mTOR) mediates Akt1 suppression of phospho-activation of S3. These and further data on Akt1-S3 binding do not support a recently proposed model that Akt blocks S3 activation through physical interaction and sequestration of S3 from TGF-beta receptors. We propose a novel model whereby Akt suppresses activation of S3 in an Akt kinase-dependent manner through mTOR, a likely route for loss of tumor suppression by TGF-beta in cancers."xsd:string |
| http://purl.uniprot.org/citations/16362038 | http://purl.org/dc/terms/identifier | "doi:10.1038/sj.emboj.7600917"xsd:string |
| http://purl.uniprot.org/citations/16362038 | http://purl.uniprot.org/core/author | "Wang H."xsd:string |
| http://purl.uniprot.org/citations/16362038 | http://purl.uniprot.org/core/author | "Song K."xsd:string |
| http://purl.uniprot.org/citations/16362038 | http://purl.uniprot.org/core/author | "Danielpour D."xsd:string |
| http://purl.uniprot.org/citations/16362038 | http://purl.uniprot.org/core/author | "Krebs T.L."xsd:string |
| http://purl.uniprot.org/citations/16362038 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16362038 | http://purl.uniprot.org/core/name | "EMBO J"xsd:string |
| http://purl.uniprot.org/citations/16362038 | http://purl.uniprot.org/core/pages | "58-69"xsd:string |
| http://purl.uniprot.org/citations/16362038 | http://purl.uniprot.org/core/title | "Novel roles of Akt and mTOR in suppressing TGF-beta/ALK5-mediated Smad3 activation."xsd:string |
| http://purl.uniprot.org/citations/16362038 | http://purl.uniprot.org/core/volume | "25"xsd:string |
| http://purl.uniprot.org/citations/16362038 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16362038 |
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