Smad2和Smad3是TGF-β信号传导通路中重要的信号传导因子，这些活性转录因子在细胞核内被去磷酸化后将被运至细胞核外，从而终止该信号通路。在本研究论文中，冯新华课题组在前期工作的基础上，对Smad2/3的核输出机理进行深入的探讨，研究鉴定了RanBP3的第58位丝氨酸被蛋白磷酸酶PPM1A去磷酸化，从而促进其协助Smad2/Smad3的核输出以及TGF-β信号通路的终止。
PPM1A dephosphorylates RanBP3 to enable efficient nuclear export of Smad2 and Smad3.
（EMBO reports,published online 30 September 2011）
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.
