蛋白磷酸酶2A的两个高度相关的调节亚基对转化生长因子-β/激活素/节点信号传导具有相反的作用。
Two highly related regulatory subunits of PP2A exert opposite effects on TGF-beta/Activin/Nodal signalling.
作者信息
Batut Julie, Schmierer Bernhard, Cao Jing, Raftery Laurel A, Hill Caroline S, Howell Michael
机构信息
Laboratory of Developmental Signalling, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
出版信息
Development. 2008 Sep;135(17):2927-37. doi: 10.1242/dev.020842.
Abstract
We identify Balpha (PPP2R2A) and Bdelta (PPP2R2D), two highly related members of the B family of regulatory subunits of the protein phosphatase PP2A, as important modulators of TGF-beta/Activin/Nodal signalling that affect the pathway in opposite ways. Knockdown of Balpha in Xenopus embryos or mammalian tissue culture cells suppresses TGF-beta/Activin/Nodal-dependent responses, whereas knockdown of Bdelta enhances these responses. Moreover, in Drosophila, overexpression of Smad2 rescues a severe wing phenotype caused by overexpression of the single Drosophila PP2A B subunit Twins. We show that, in vertebrates, Balpha enhances TGF-beta/Activin/Nodal signalling by stabilising the basal levels of type I receptor, whereas Bdelta negatively modulates these pathways by restricting receptor activity. Thus, these highly related members of the same subfamily of PP2A regulatory subunits differentially regulate TGF-beta/Activin/Nodal signalling to elicit opposing biological outcomes.
摘要
我们鉴定出蛋白磷酸酶PP2A调节亚基B家族的两个高度相关成员Bα（PPP2R2A）和Bδ（PPP2R2D），它们是TGF-β/激活素/节点信号传导的重要调节因子，以相反的方式影响该信号通路。在非洲爪蟾胚胎或哺乳动物组织培养细胞中敲低Bα会抑制TGF-β/激活素/节点依赖性反应，而敲低Bδ则会增强这些反应。此外，在果蝇中，Smad2的过表达挽救了由单一果蝇PP2A B亚基Twins过表达引起的严重翅膀表型。我们表明，在脊椎动物中，Bα通过稳定I型受体的基础水平来增强TGF-β/激活素/节点信号传导，而Bδ则通过限制受体活性来负调节这些信号通路。因此，PP2A调节亚基同一亚家族的这些高度相关成员以不同方式调节TGF-β/激活素/节点信号传导，以引发相反的生物学结果。
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