{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:17:35Z","timestamp":1791137855091,"version":"4.1.0"},"reference-count":41,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2012,3,1]]},"abstract":"<jats:p> 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-\u03b2-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<jats:sup>\u2212\/\u2212<\/jats:sup> 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. <\/jats:p>","DOI":"10.1152\/ajpcell.00379.2011","type":"journal-article","created":{"date-parts":[[2011,12,8]],"date-time":"2011-12-08T07:38:01Z","timestamp":1323329881000},"page":"C804-C820","source":"Crossref","is-referenced-by-count":56,"title":["Nongenomic STAT5-dependent effects on Golgi apparatus and endoplasmic reticulum structure and function"],"prefix":"10.1152","volume":"302","author":[{"given":"Jason E.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Anatomy, New York Medical College, Valhalla;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang-Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, New York Medical College, Valhalla;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Xia","family":"Liang","sequence":"additional","affiliation":[{"name":"OCS Microscopy Core and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Gough","sequence":"additional","affiliation":[{"name":"Department of Pathology and New York University Cancer Institute, New York University School of Medicine, New York; 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