Edlund Sofia, Landström Maréne, Heldin Carl-Henrik, Aspenström Pontus
Ludwig Institute for Cancer Research, Biomedical Center, Box 595, 751 24 Uppsala, Sweden.
J Cell Sci. 2004 Apr 1;117(Pt 9):1835-47. doi: 10.1242/jcs.01036.
Transforming growth factor beta (TGF-beta) is a potent regulator of cell growth and differentiation in many cell types. The Smad signaling pathway constitutes a main signal transduction route downstream of TGF-beta receptors. The inhibitory Smads, Smad6 and Smad7, are considered to function as negative regulators of the TGF-beta/Smad signaling cascade. In a previous study, we found that TGF-beta induces rearrangements of the actin filament system in human prostate carcinoma cells and that this response requires the small GTPases Cdc42 and RhoA. On the basis of the current view on the function of Smad7 in TGF-beta signaling, we hypothesized that Smad7 would function as a negative regulator of the TGF-beta-induced activation of Cdc42 and RhoA, but instead we found that the reverse is the case; Smad7 is required for the TGF-beta-induced activation of Cdc42 and the concomitant reorganization of the actin filament system. These observations propose a novel role for Smad7 in TGF-beta-dependent activation of Rho GTPases.
转化生长因子β（TGF-β）是多种细胞类型中细胞生长和分化的有效调节因子。Smad信号通路构成了TGF-β受体下游的主要信号转导途径。抑制性Smad蛋白Smad6和Smad7被认为是TGF-β/Smad信号级联反应的负调节因子。在先前的一项研究中，我们发现TGF-β可诱导人前列腺癌细胞中肌动蛋白丝系统的重排，并且这种反应需要小GTP酶Cdc42和RhoA。基于目前对Smad7在TGF-β信号传导中功能的认识，我们推测Smad7会作为TGF-β诱导的Cdc42和RhoA激活的负调节因子，但相反我们发现事实并非如此；Smad7是TGF-β诱导的Cdc42激活以及伴随的肌动蛋白丝系统重组所必需的。这些观察结果提出了Smad7在TGF-β依赖性Rho GTP酶激活中的新作用。
