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http://purl.uniprot.org/citations/22159083 | http://www.w3.org/2000/01/rdf-schema#comment | "We report unexpected nongenomic functions of signal transducer and activator of transcription (STAT) 5 species in the cytoplasm aimed at preserving the structure and function of the Golgi apparatus and rough endoplasmic reticulum (ER) in vascular cells. Immunoimaging and green fluorescent protein-tagged-STAT5a protein localization studies showed the constitutive association of nonphosphorylated STAT5a, and to a lesser extent STAT5b, with the Golgi apparatus and of STAT5a with centrosomes in human pulmonary arterial endothelial and smooth muscle cells. Acute knockdown of STAT5a/b species using small interfering RNAs (siRNAs), including in the presence of an mRNA synthesis inhibitor (5,6-dichloro-1-β-d-ribofuranosylbenzimidazole), produced a dramatic phenotype within 1 day, consisting of dilatation and fragmentation of Golgi cisternae, a marked tubule-to-cyst change in the ER, increased accumulation of reticulon-4 (RTN4)/Nogo-B and atlastin-3 (ATL3) at cyst-zone boundaries, cystic separation of the outer and inner nuclear membranes, accompanied by scalloped/lunate distortion of the nucleus, with accumulation of RTN4 on convex sides of distorted nuclei. These cells showed inhibition of vesicular stomatitis virus G protein glycoprotein trafficking, mitochondrial fragmentation, and reduced mitochondrial function. STAT5a/b(-/-) mouse embryo fibroblasts also showed altered ER/Golgi dynamics. RTN4 knockdown using siRNA did not affect development of the cystic phenotype; ATL3 siRNA led to effacement of cyst-zone boundaries. In magnetic-bead cross-immunopanning assays, ATL3 bound both STAT5a and STAT5b. Remarkably, this novel cystic ER/lunate nucleus phenotype was characteristic of vascular cells in arterial lesions of idiopathic pulmonary hypertension, an unrelentingly fatal human disease. These data provide evidence of a STAT-family protein regulating the structure of a cytoplasmic organelle and implicate this mechanism in the pathogenesis of a human disease."xsd:string |
http://purl.uniprot.org/citations/22159083 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpcell.00379.2011"xsd:string |
http://purl.uniprot.org/citations/22159083 | http://purl.uniprot.org/core/author | "Lee J.E."xsd:string |
http://purl.uniprot.org/citations/22159083 | http://purl.uniprot.org/core/author | "Levy D.E."xsd:string |
http://purl.uniprot.org/citations/22159083 | http://purl.uniprot.org/core/author | "Yang Y.M."xsd:string |
http://purl.uniprot.org/citations/22159083 | http://purl.uniprot.org/core/author | "Liang F.X."xsd:string |
http://purl.uniprot.org/citations/22159083 | http://purl.uniprot.org/core/author | "Sehgal P.B."xsd:string |
http://purl.uniprot.org/citations/22159083 | http://purl.uniprot.org/core/author | "Gough D.J."xsd:string |
http://purl.uniprot.org/citations/22159083 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
http://purl.uniprot.org/citations/22159083 | http://purl.uniprot.org/core/name | "Am J Physiol Cell Physiol"xsd:string |
http://purl.uniprot.org/citations/22159083 | http://purl.uniprot.org/core/pages | "C804-20"xsd:string |
http://purl.uniprot.org/citations/22159083 | http://purl.uniprot.org/core/title | "Nongenomic STAT5-dependent effects on Golgi apparatus and endoplasmic reticulum structure and function."xsd:string |
http://purl.uniprot.org/citations/22159083 | http://purl.uniprot.org/core/volume | "302"xsd:string |
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