| http://purl.uniprot.org/citations/25614622 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25614622 | http://www.w3.org/2000/01/rdf-schema#comment | "We have recently demonstrated that the PI3K class II-α isoform (PI3K-C2α), which generates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,4-bisphosphates, plays crucial roles in angiogenesis, by analyzing PI3K-C2α knock-out mice. The PI3K-C2α actions are mediated at least in part through its participation in the internalization of VEGF receptor-2 and sphingosine-1-phosphate receptor S1P1 and thereby their signaling on endosomes. TGFβ, which is also an essential angiogenic factor, signals via the serine/threonine kinase receptor complex to induce phosphorylation of Smad2 and Smad3 (Smad2/3). SARA (Smad anchor for receptor activation) protein, which is localized in early endosomes through its FYVE domain, is required for Smad2/3 signaling. In the present study, we showed that PI3K-C2α knockdown nearly completely abolished TGFβ1-induced phosphorylation and nuclear translocation of Smad2/3 in vascular endothelial cells (ECs). PI3K-C2α was necessary for TGFβ-induced increase in phosphatidylinositol 3,4-bisphosphates in the plasma membrane and TGFβ receptor internalization into the SARA-containing early endosomes, but not for phosphatidylinositol 3-phosphate enrichment or localization of SARA in the early endosomes. PI3K-C2α was also required for TGFβ receptor-mediated formation of SARA-Smad2/3 complex. Inhibition of dynamin, which is required for the clathrin-dependent receptor endocytosis, suppressed both TGFβ receptor internalization and Smad2/3 phosphorylation. TGFβ1 stimulated Smad-dependent VEGF-A expression, VEGF receptor-mediated EC migration, and capillary-like tube formation, which were all abolished by either PI3K-C2α knockdown or a dynamin inhibitor. Finally, TGFβ1-induced microvessel formation in Matrigel plugs was greatly attenuated in EC-specific PI3K-C2α-deleted mice. These observations indicate that PI3K-C2α plays the pivotal role in TGFβ receptor endocytosis and thereby Smad2/3 signaling, participating in angiogenic actions of TGFβ."xsd:string |
| http://purl.uniprot.org/citations/25614622 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m114.601484"xsd:string |
| http://purl.uniprot.org/citations/25614622 | http://purl.uniprot.org/core/author | "Yoshioka K."xsd:string |
| http://purl.uniprot.org/citations/25614622 | http://purl.uniprot.org/core/author | "Okamoto Y."xsd:string |
| http://purl.uniprot.org/citations/25614622 | http://purl.uniprot.org/core/author | "Aki S."xsd:string |
| http://purl.uniprot.org/citations/25614622 | http://purl.uniprot.org/core/author | "Takuwa Y."xsd:string |
| http://purl.uniprot.org/citations/25614622 | http://purl.uniprot.org/core/author | "Takuwa N."xsd:string |
| http://purl.uniprot.org/citations/25614622 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25614622 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/25614622 | http://purl.uniprot.org/core/pages | "6086-6105"xsd:string |
| http://purl.uniprot.org/citations/25614622 | http://purl.uniprot.org/core/title | "Phosphatidylinositol 3-kinase class II alpha-isoform PI3K-C2alpha is required for transforming growth factor beta-induced Smad signaling in endothelial cells."xsd:string |
| http://purl.uniprot.org/citations/25614622 | http://purl.uniprot.org/core/volume | "290"xsd:string |
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