Smad function and intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription.

Afzal F; Pratap J; Ito KIto YStein JLvan Wijnen AJStein GSLian JBJaved A

首页> 外文期刊>Journal of Cellular Physiology >Smad function and intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription.

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Smad function and intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription.

机译：Smad函数和在细胞核内的目标Runx2成骨的血统所需图案诱导和BMP2响应转录。

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The coordinated activity of Runx2 and BMP/TGFbeta-activated Smads is critical for formation of the skeleton, but the precise structural basis for the Runx2/Smad interaction has not been resolved. By deletion mutagenesis, we have defined the Runx2 motif required for physical and functional interaction with either BMP or TGFbeta responsive Smads. Smad responsive transcriptional activity was retained upon deletion of the C-terminus to amino acid (aa) 432 but lost with deletion to aa 391. Thus the Smad interacting domain (SMID) of Runx2 (432-391) is embedded in the well-defined nuclear matrix targeting signal (NMTS) that mediates intranuclear trafficking. The SMID suffices as an interacting module when fused to the heterologous Gal-4 protein. Formation of the Runx2 and Smad complex is dependent on Runx2 phosphorylation through the MAPK signaling pathway, as determined by co-immunoprecipitation studies. We established that all SMID/NMTS deficient Runx2 mutants do not show in situ association with Smad in the nucleus nor do they support BMP2-mediated osteogenic induction of the mesenchymal C2C12 cell line. Thus, we provide direct evidence that the SMID/NMTS domain (391-432) of Runx2 is essential for BMP2-mediated osteoblast differentiation. Our findings suggest that TGFbeta/ BMP2 signaling, MAPK dependent phosphorylation, and Runx2 subnuclear targeting converge to induce the osteogenic phenotype.

机译：Runx2的协调活动BMP / TGFbeta-activated Smads是至关重要的形成的骨架,但精确结构性基础Runx2 / Smad交互还没有解决。我们已经定义了所需Runx2的主题物理和功能相互作用BMP或Smads TGFbeta敏感。转录活动保留删除糖基的氨基酸(aa) 432但失去了删除391 aa。相互作用域(先进)Runx2 (432 - 391)嵌入在定义良好的核矩阵目标(nmt)介导的信号在细胞核内的交易。当融合不同的交互模块Gal-4蛋白质。复杂的依赖Runx2磷酸化通过MAPK信号通路,如确定由co-immunoprecipitation研究。所有萧述三/ nmt缺乏Runx2突变体显示原位协会与Smad细胞核他们也不支持BMP2-mediated成骨感应的间叶细胞C2C12细胞线。因此,我们提供了直接的证据萧述三/ nmt Runx2的域(391 - 432)是至关重要的对于BMP2-mediated成骨细胞分化。研究结果表明,TGFbeta / BMP2信号,MAPK依赖磷酸化,Runx2亚核的收敛于目标引起的成骨表型。

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来源
《Journal of Cellular Physiology》 |2005年第1期|63-72|共10页
作者
Afzal F; Pratap J; Ito KIto YStein JLvan Wijnen AJStein GSLian JBJaved A;
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Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA.;

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正文语种英语
中图分类细胞生物学;
关键词
Bone Cell; Bone Morphogenetic Proteins; RUNX2 genePhosphoproteinsMAPK Signaling PathwayCo-ImmunoprecipitationTransforming Growth Factor betaBMP2 geneDNA-Binding Proteinstargeting;

机译：骨细胞,骨形成蛋白;RUNX2genePhosphoproteinsMAPK信号PathwayCo-ImmunoprecipitationTransforming增长因素betaBMP2 geneDNA-Binding Proteinstargeting;

Smad function and intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription.

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