http://purl.uniprot.org/citations/19218245 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/19218245 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/19218245 | http://www.w3.org/2000/01/rdf-schema#comment | "Smad proteins transduce the transforming growth factor-beta (TGF-beta) signal at the cell surface into gene regulation in the nucleus. Upon TGF-beta treatment, the highly homologous Smad2 and Smad3 are phosphorylated by the TGF-beta receptor at the SSXS motif in the C-terminal tail. Here we show that in addition to the C-tail, three (S/T)-P sites in the Smad3 linker region, Ser(208), Ser(204), and Thr(179) are phosphorylated in response to TGF-beta. The linker phosphorylation peaks at 1 h after TGF-beta treatment, behind the peak of the C-tail phosphorylation. We provide evidence suggesting that the C-tail phosphorylation by the TGF-beta receptor is necessary for the TGF-beta-induced linker phosphorylation. Although the TGF-beta receptor is necessary for the linker phosphorylation, the receptor itself does not phosphorylate these sites. We further show that ERK is not responsible for TGF-beta-dependent phosphorylation of these three sites. We show that GSK3 accounts for TGF-beta-inducible Ser(204) phosphorylation. Flavopiridol, a pan-CDK inhibitor, abolishes TGF-beta-induced phosphorylation of Thr(179) and Ser(208), suggesting that the CDK family is responsible for phosphorylation of Thr(179) and Ser(208) in response to TGF-beta. Mutation of the linker phosphorylation sites to nonphosphorylatable residues increases the ability of Smad3 to activate a TGF-beta/Smad-target gene as well as the growth-inhibitory function of Smad3. Thus, these observations suggest that TGF-beta-induced phosphorylation of Smad3 linker sites inhibits its antiproliferative activity."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m809281200"xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m809281200"xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/author | "Liu F."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/author | "Liu F."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/author | "Wang G."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/author | "Wang G."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/author | "He D."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/author | "He D."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/author | "Matsuura I."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/author | "Matsuura I."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/pages | "9663-9673"xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/pages | "9663-9673"xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/title | "Transforming growth factor-{beta}-inducible phosphorylation of Smad3."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/title | "Transforming growth factor-{beta}-inducible phosphorylation of Smad3."xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/volume | "284"xsd:string |
http://purl.uniprot.org/citations/19218245 | http://purl.uniprot.org/core/volume | "284"xsd:string |
http://purl.uniprot.org/citations/19218245 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19218245 |
http://purl.uniprot.org/citations/19218245 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19218245 |