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-β) and TGF-β-related proteins. Accumulating evidence demonstrates that Smads possess intrinsic nucleocytoplasmic shuttling capacity, which enables them to transmit TGF-β 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-β signaling.
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Acknowledgments
We thank members of Feng and Lin labs for their contributions to the original research and helpful discussion. The described research is supported by NIH grants (R01AR053591 and R01CA108454 to X.-H.F., R01DK073932 to X.L.) and a Leukemia and Lymphoma Society Scholar Award (X.-H.F.).
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Dai, F., Duan, X., Liang, YY., Lin, X., Feng, XH. (2010). Coupling of Dephosphorylation and Nuclear Export of Smads in TGF-β Signaling. In: Higgins, P. (eds) Transcription Factors. Methods in Molecular Biology, vol 647. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-738-9_7
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DOI: https://doi.org/10.1007/978-1-60761-738-9_7
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