title: Coupling of dephosphorylation and nuclear export of Smads in TGF-beta signaling.
abstract: In eukaryotes, regulation of signaling mediators/effectors in the nucleus is one of the principal mechanisms that govern duration and strength of signaling. Smads are a family of structurally related intracellular proteins that serve as signaling effectors for transforming growth factor beta (TGF-beta) and TGF-beta-related proteins. Accumulating evidence demonstrates that Smads possess intrinsic nucleocytoplasmic shuttling capacity, which enables them to transmit TGF-beta signals from cell membrane to nucleus. We recently identified two important steps in the termination of nuclear Smad signaling. The first step is initiated by a serine/threonine phosphatase PPM1A that dephosphorylates Smad2/3 in the nucleus, thereby shutting down signaling capacity of phosphorylated Smad2/3. The second step involves nuclear export of dephosphorylated Smad2/3 with the aid of nuclear protein RanBP3 to terminate Smad signaling. This chapter introduces methods for examining nuclear export of Smad2/3 in TGF-beta signaling.
authors.affiliation: Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Fangyan
authors.initials: F
authors.lastname: Dai
authors.forename: Xueyan
authors.initials: X
authors.lastname: Duan
authors.forename: Yao-Yun
authors.initials: YY
authors.lastname: Liang
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; D002458:Cell Fractionation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D010744:Phosphoric Monoester Hydrolases