title: PPM1A dephosphorylates RanBP3 to enable efficient nuclear export of Smad2 and Smad3.
abstract: Smad2 and Smad3 (Smad2/3) are essential signal transducers and transcription factors in the canonical transforming growth factor-β (TGF-β) signalling pathway. Active Smad2/3 signalling in the nucleus is terminated by dephosphorylation and subsequent nuclear export of Smad2/3. Here we report that protein phosphatase PPM1A regulates the nuclear export of Smad2/3 through targeting nuclear exporter RanBP3. PPM1A directly interacted with and dephosphorylated RanBP3 at Ser 58 in vitro and in vivo. Consistently, RanBP3 phosphorylation was elevated in PPM1A-null mouse embryonic fibroblasts. Dephosphorylation of RanBP3 at Ser 58 promoted its ability to export Smad2/3 and terminate TGF-β responses. Our findings indicate the critical role of PPM1A in maximizing exporter activity of RanBP3 for efficient termination of canonical TGF-β signalling.
authors.affiliation: Department of Molecular & Cellular Biology, Texas A&M Health Sciences Center, Houston, Texas 77030, USA.
authors.forename: Fangyan
authors.initials: F
authors.lastname: Dai
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Li
authors.forename: Xia
authors.initials: X
authors.lastname: Lin
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Feng
mesh_terms: D021581:Active Transport, Cell Nucleus; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D000071636:Protein Phosphatase 2C; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D013379:Substrate Specificity; D016212:Transforming Growth Factor beta
chemical_list: D050505:Mutant Proteins; D009687:Nuclear Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; C000607456:PPM1A protein, human; D010749:Phosphoprotein Phosphatases; C000607466:Ppm1a protein, mouse; D000071636:Protein Phosphatase 2C