title: Prostaglandin E2 modifies SMAD2 and promotes SMAD2-SMAD4 complex formation.
abstract: We report that PGE2 promotes Smad2-Smad4 complex formation and this phenomenon could be blocked by DIDS, an anion transporter inhibitor. Our data suggest that PGE2 had no effects on Smad2 phosphorylation, suggesting that PGE2-mediated Smad2-Smad4 complex formation is independent of TGF-β signaling and that PGE2 induced Smad2 modification which is different from TGF-β-mediated phosphorylation. We demonstrate that in primary human glomerular mesangial cells PGE2 caused modification of Smad2 as detected by Smad2N antibody, raised against a peptide near the N-terminus of Smad2. We hypothesize that Smad2 protein is post-translationaly modified by PGE2. Direct evidence of Smad2 modification by PGE2 was achieved by avidin pulldown assay which showed that endogenous Smad2 and recombinant Smad2 protein were attached by biotin-labeled PGE2. Taken together, our results provided evidence that post-translational modification of Smad2 could be a mechanism for the action of PGE2 in the pathogenesis of human pathologies.
authors.affiliation: Division of Nephrology and Kidney Disease Center, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Molecular Genetics, 8701 Watertown Plank Road, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Division of Nephrology and Kidney Disease Center, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: sorokin@mcw.edu.
authors.forename: Andrey
authors.initials: A
authors.lastname: Sorokin
mesh_terms: D002478:Cells, Cultured; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050527:Mesangial Cells / Q000378:metabolism* / Q000473:pathology; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; C497782:SMAD2 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; D015232:Dinoprostone
keywords: Mesangial cells; Prostaglandins; Signaling