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Mol Cell Biol
2005 Nov 01;2522:9845-58. doi: 10.1128/MCB.25.22.9845-9858.2005.
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Kinetic analysis of Smad nucleocytoplasmic shuttling reveals a mechanism for transforming growth factor beta-dependent nuclear accumulation of Smads.
Schmierer B
,
Hill CS
.
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Upon transforming growth factor beta (TGF-beta) stimulation, Smads accumulate in the nucleus, where they regulate gene expression. Using fluorescence perturbation experiments on Smad2 and Smad4 fused to either enhanced green fluorescent protein or photoactivatable green fluorescent protein, we have studied the kinetics of Smad nucleocytoplasmic shuttling in a quantitative manner in vivo. We have obtained rate constants for import and export of Smad2 and show that the cytoplasmic localization of Smad2 in uninduced cells reflects its nuclear export being more rapid than import. We find that TGF-beta-induced nuclear accumulation of Smad2 is caused by a pronounced drop in the export rate of Smad2 from the nucleus, which is associated with a strong decrease in nuclear mobility of Smad2 and Smad4. TGF-beta-induced nuclear accumulation involves neither a release from cytoplasmic retention nor an increase in Smad2 import rate. Hence, TGF-beta-dependent nuclear accumulation of Smad2 is caused exclusively by selective nuclear trapping of phosphorylated, complexed Smad2. The proposed mechanism reconciles signal-dependent nuclear accumulation of Smad2 with its continuous nucleocytoplasmic cycling properties.
Angel,
12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5'-flanking region.
1987, Pubmed
Angel,
12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5'-flanking region.
1987,
Pubmed
Chen,
Nuclear targeting of transforming growth factor-beta-activated Smad complexes.
2005,
Pubmed
De Bosscher,
Molecular and functional consequences of Smad4 C-terminal missense mutations in colorectal tumour cells.
2004,
Pubmed
,
Xenbase
Germain,
Homeodomain and winged-helix transcription factors recruit activated Smads to distinct promoter elements via a common Smad interaction motif.
2000,
Pubmed
,
Xenbase
Hager,
Protein dynamics in the nuclear compartment.
2002,
Pubmed
Inman,
SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7.
2002,
Pubmed
Inman,
Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity.
2002,
Pubmed
Kurisaki,
Transforming growth factor-beta induces nuclear import of Smad3 in an importin-beta1 and Ran-dependent manner.
2001,
Pubmed
Laping,
Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB-431542.
2002,
Pubmed
Nicolás,
Attenuation of the TGF-beta-Smad signaling pathway in pancreatic tumor cells confers resistance to TGF-beta-induced growth arrest.
2003,
Pubmed
Nicolás,
Analysis of Smad nucleocytoplasmic shuttling in living cells.
2004,
Pubmed
Patterson,
A photoactivatable GFP for selective photolabeling of proteins and cells.
2002,
Pubmed
Pierreux,
Transforming growth factor beta-independent shuttling of Smad4 between the cytoplasm and nucleus.
2000,
Pubmed
,
Xenbase
Randall,
Different Smad2 partners bind a common hydrophobic pocket in Smad2 via a defined proline-rich motif.
2002,
Pubmed
,
Xenbase
Randall,
Recognition of phosphorylated-Smad2-containing complexes by a novel Smad interaction motif.
2004,
Pubmed
Ribbeck,
Kinetic analysis of translocation through nuclear pore complexes.
2001,
Pubmed
Shi,
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
2003,
Pubmed
Sprague,
FRAP analysis of binding: proper and fitting.
2005,
Pubmed
Swanson,
Cellular dimensions affecting the nucleocytoplasmic volume ratio.
1991,
Pubmed
Watanabe,
Regulation of intracellular dynamics of Smad4 by its leucine-rich nuclear export signal.
2000,
Pubmed
Wu,
Formation of a stable heterodimer between Smad2 and Smad4.
2001,
Pubmed
Xiao,
An extended bipartite nuclear localization signal in Smad4 is required for its nuclear import and transcriptional activity.
2003,
Pubmed
Xiao,
Importin beta mediates nuclear translocation of Smad 3.
2000,
Pubmed
Xu,
The nuclear import function of Smad2 is masked by SARA and unmasked by TGFbeta-dependent phosphorylation.
2000,
Pubmed
Xu,
Smad2 nucleocytoplasmic shuttling by nucleoporins CAN/Nup214 and Nup153 feeds TGFbeta signaling complexes in the cytoplasm and nucleus.
2002,
Pubmed
Xu,
Distinct domain utilization by Smad3 and Smad4 for nucleoporin interaction and nuclear import.
2003,
Pubmed
Xu,
Nucleocytoplasmic shuttling of signal transducers.
2004,
Pubmed
