Multiple signaling pathways converge on the Cbfa1/Runx2 transcription factor to regulate osteoblast differentiation
Multiple signaling pathways converge on the Cbfa1/Runx2 transcription factor to regulate osteoblast differentiation
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DOI：
10.1080/03008200390152188
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发表时间：
2003-01-01
影响因子：
2.9
通讯作者：
Reith, E
中科院分区：
文献类型：
--
作者：
Franceschi, RT;Xiao, GZ;Reith, E
Cbfa1/Runx2转录因子是成骨细胞分化所必需的。然而，Runx2的水平通常与其转录活性没有很好的相关性，这表明该因子必须通过共价修饰或通过与其他核成分的相互作用来激活。Runx2被丝裂原活化蛋白激酶(MAPK)途径磷酸化并激活。这一途径至少通过两种方式被刺激：通过I型胶原与成骨细胞表面的α(2)β(1)整合素结合，以及通过成骨生长因子FGF2处理细胞。蛋白激酶A(PKA)在一定条件下也可以磷酸化/激活Runx2。Runx2的活性也被已知刺激特定信号转导途径的因素所增强，如PTH/PTHrP(通过PKA和PKC途径的信号)和BMPs(通过Smad蛋白的信号)。与Runx2的相互作用是复杂的，既涉及不同成分的结合，如AP-1因子和Smads以分离DNA上的位置，Runx2与AP-1/Smad因子之间的直接相互作用，以及MAPK或PKA依赖的Runx2的磷酸化。这些发现表明，Runx2在协调涉及成骨细胞分化的多个信号方面发挥着核心作用。
The Cbfa1/Runx2 transcription factor is essential for osteoblast differentiation. However, levels of Runx2 are often not well correlated with its transcriptional activity suggesting that this factor must be activated either by covalent modification or through interactions with other nuclear components. Runx2 is phosphorylated and activated by the mitogen-activated protein kinase (MAPK) pathway. This pathway is stimulated in at least two ways: by binding of type I collagen to alpha(2)beta(1) integrins on the osteoblast surface and by treatment of cells with the osteogenic growth factor, FGF2. Protein kinase A (PKA) also may phosphorylate/activate Runx2 under certain conditions. Runx2 activity also is enhanced by factors known to stimulate specific signal transduction pathways such as PTH/PTHrP (signals through PKA and PKC pathways) and BMPs (Signal through Smad proteins). Interactions with Runx2 are complex involving both binding of distinct components such as AP-1 factors and Smads to separate sites on DNA, direct interactions between Runx2 and AP-1/Smad factors and MAPK or PKA-dependent Runx2 phosphorylation. These findings suggest that Runx2 plays a central role in coordinating multiple signals involved in osteoblast differentiation.