Maduzia L L, Padgett R W
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08855, USA.
Biochem Biophys Res Commun. 1997 Sep 18;238(2):595-8. doi: 10.1006/bbrc.1997.7353.
Smads are a novel group of proteins which act to mediate signaling by members of the TGF-beta superfamily. Seven vertebrate Smad genes, which fall into three classes, have been reported. Members of the Class I Smads have been shown to bind to the cytoplasmic portion of the TGF-beta like receptors, where they become phosphorylated and translocate to the nucleus. Once in the nucleus they may function as transcriptional activators. We wondered if translocation to the nucleus is a general property of the Smads and whether it was evolutionarily conserved. We examined the subcellular localization of Drosophila MAD and found that it is capable of nuclear translocation, in Drosophila S2 cells, when the dpp pathway is stimulated. To prove the functional conservation of receptor/Smad interactions, we used the mouse BMP type I receptor ALK6 to stimulate the pathway and found that it is capable of sending MAD to the nucleus. These results show that cytoplasmic localization with translocation to the nucleus upon stimulation is a feature of the Smads that is conserved through evolution.
Smads是一类新型蛋白质，其作用是介导转化生长因子-β（TGF-β）超家族成员的信号传导。据报道，有七个脊椎动物Smad基因，分为三类。I类Smads成员已被证明可与TGF-β样受体的细胞质部分结合，在那里它们被磷酸化并转运到细胞核。一旦进入细胞核，它们可能作为转录激活因子发挥作用。我们想知道转运到细胞核是否是Smads的普遍特性，以及它在进化上是否保守。我们研究了果蝇MAD的亚细胞定位，发现当dpp途径被激活时，它在果蝇S2细胞中能够进行核转运。为了证明受体/Smad相互作用的功能保守性，我们使用小鼠BMP I型受体ALK6来激活该途径，发现它能够将MAD转运到细胞核。这些结果表明，刺激后从细胞质定位转运到细胞核是Smads的一个特征，并且在进化过程中是保守的。
