TGFβ通路作为一条重要的信号转导途径在细胞增殖、分化及体内组织器官发育的过程中起关键作用。一般认为，TGFβ信号是通过其受体的丝-苏氨酸蛋白激酶活性，催化下游效应分子Smad2或Smad3磷酸化，磷酸化后的Smad2/3从胞浆转位到胞核，进而作为转录因子调控靶基因的表达。我们的研究发现在没有外在TGFβ作用的条件下，Smad2主要分布于胞浆，而Smad3主要分布于胞核。更重要的是TGFβ及Smad羧基末端的磷酸化只能调控全长Smad2的核浆分布，而不影响Smad3的分布。因而我们认为和传统的理论一致，Smad2通过胞浆-胞核转位介导了TGFβ的信号，而Smad3可能存在TGFβ信号非依赖的生理功能。研究清楚TGFβ非依赖Smad3胞核分布的分子机制及其潜在的生理功能是对当前TGFβ这一传统的信号通路的有力补充。

TGFβ signaling is one of the most important signaling pathways that plays a crucial function in cell proliferation, differentiation and early embryonic development. In general, it has been well proposed that Smad2/Smad3 are two downstream effectors of TGFβ signaling. Activated TGFβ receptor phosphorylates the c-terminal tail of Smad2/Smad3, which in turn homodimerizes, binds to Smad4 and finally translocates to the nucleus as a complex. Where in the nucleus, the protein complex acts as a transcription factor and regulates target gene expression. Our recent preliminary experiments find that in contrast to the full length Smad2 which is distributed in the cytoplasm, Smad3 is preferentially distributed in the nucleus. More importantly, different from full length Smad2, the nuclear distribution of Smad3 does not depend on TGFβ signaling and Smad c-terminal phosphorylation. Therefore, we propose that Smad2/Smad3 may exert their functional role through either a TGFβ dependent- or independent-manner. Dissection out these detailed mechanisms will thus greatly improve our understanding about the widely-studied TGFβ signaling pathway.