Nakao A, Röijer E, Imamura T, Souchelnytskyi S, Stenman G, Heldin C H, ten Dijke P
Ludwig Institute for Cancer Research, Box 595, S-751 24 Uppsala, Sweden.
J Biol Chem. 1997 Jan 31;272(5):2896-900. doi: 10.1074/jbc.272.5.2896.
Transforming growth factor-beta (TGF-beta) superfamily members are multifunctional cytokines that exert their effects via heteromeric complexes of two distinct serine and threonine kinase receptors. Drosophila mothers against decapentaplegic and related genes in Caenorhabditis elegans, Xenopus, and mammals were shown to function downstream in the intracellular signaling pathways of TGF-beta superfamily members. Here we report the cloning of a Mad-related protein, termed Sma- and Mad-related protein 2 (Smad2). TGF-beta stimulated the phosphorylation and nuclear translocation of Smad2 in nontransfected Mv1Lu cells. In addition, we demonstrated that TGF-beta and activin mediated phosphorylation of Smad2 after its overexpression with appropriate type I and II receptors in COS cells. Smad2 and Smad1 were found to be broadly expressed in human tissues. Smad2 is closely linked to DPC4 on chromosome 18q21.1, a region often deleted in human cancers. Cells that lack Smad2 may escape from TGF-beta-mediated growth inhibition and promote cancer progression.
转化生长因子-β（TGF-β）超家族成员是多功能细胞因子，它们通过两种不同的丝氨酸和苏氨酸激酶受体的异源复合物发挥作用。果蝇中与抗去五体不全蛋白相关的基因以及秀丽隐杆线虫、非洲爪蟾和哺乳动物中的相关基因，被证明在TGF-β超家族成员的细胞内信号通路中发挥下游作用。在此，我们报告一种与Mad相关的蛋白的克隆，称为Sma和Mad相关蛋白2（Smad2）。TGF-β刺激未转染的Mv1Lu细胞中Smad2的磷酸化和核转位。此外，我们证明在COS细胞中与适当的I型和II型受体共表达后，TGF-β和激活素介导Smad2的磷酸化。发现Smad2和Smad1在人体组织中广泛表达。Smad2与18q21.1染色体上的DPC4紧密相连，该区域在人类癌症中常发生缺失。缺乏Smad2的细胞可能逃避TGF-β介导的生长抑制并促进癌症进展。
