BMP-2 诱导的osterix 表达中磷脂酰肌醇 3-激酶、Akt 激酶和 Smad 信号通路的整合。
Integration of phosphatidylinositol 3-kinase, Akt kinase, and Smad signaling pathway in BMP-2-induced osterix expression.
机构信息
Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
出版信息
Calcif Tissue Int. 2010 Dec;87(6):533-40. doi: 10.1007/s00223-010-9419-3. Epub 2010 Sep 26.
Abstract
Osterix (Osx), a BMP-2-regulated transcription factor, controls expression of genes essential for osteoblast differentiation. Using progressive deletion of the Osx promoter, we characterized a Smad binding element (SBE) between -552 and -839 bp from its transcription start site. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed binding and in vivo recruitment of Smads 1 and 5 to the Osx SBE. Inactivation of PI 3-kinase by the pharmacologic inhibitor Ly294002 or by dominant negative (DN) enzyme significantly blocked BMP-2-induced Osx protein and mRNA expression and Osx transcription. Finally, both DN PI 3-kinase and DN Akt significantly attenuated Smad 5-dependent transcription of Osx, demonstrating the first evidence for a concerted action of PI 3-kinase/Akt signaling with BMP-specific Smads for expression of Osx.
摘要
osterix(Osx)是一种 bmp-2 调控的转录因子，控制着成骨细胞分化所必需的基因的表达。通过渐进式删除 Osx 启动子，我们从其转录起始位点到-552bp 到-839bp 之间鉴定了一个 Smad 结合元件(SBE)。电泳迁移率变动分析和染色质免疫沉淀分析显示 Smads1 和 5 结合并在体内募集到 Osx SBE。通过药理学抑制剂 Ly294002 或显性负性(dn)酶失活 PI 3-激酶显著阻断了 BMP-2 诱导的 Osx 蛋白和 mRNA 表达以及 Osx 转录。最后，dn PI 3-激酶和 dn Akt 显著减弱了 Smad5 依赖的 Osx 转录，这首次证明了 PI 3-激酶/akt 信号与 BMP 特异性 Smads 协同作用以表达 Osx。
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