Smads, TAK1, and their common target ATF-2 play a critical role in cardiomyocyte differentiation.
Smads, TAK1, and their common target ATF-2 play a critical role in cardiomyocyte differentiation.
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DOI：
10.1083/jcb.153.4.687
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发表时间：
2001-05-14
期刊：
影响因子：
--
通讯作者：
Komuro I
中科院分区：
文献类型：
--
作者：
Monzen K;Hiroi Y;Kudoh S;Akazawa H;Oka T;Takimoto E;Hayashi D;Hosoda T;Kawabata M;Miyazono K;Ishii S;Yazaki Y;Nagai R;Komuro I
我们以前证明，骨形态发生蛋白（BMP）诱导心肌细胞分化通过丝裂原活化蛋白激酶TAK 1。转录因子Smads介导转化生长因子-β信号传导，ATF/CREB家族转录因子ATF-2最近已被证明是Smad和TAK 1通路的共同靶标。我们在这里研究了Smads和ATF-2在P19 CL 6（鼠P19细胞的克隆衍生物）心肌细胞分化中的作用。虽然P19 CL 6有效地分化成心肌细胞时，用二甲基亚砜，P19 CL 6头蛋白，组成型过表达的BMP拮抗剂头蛋白的P19 CL 6细胞系，没有分化成心肌细胞。Smad 1，配体特异性的Smad，和Smad 4，一个共同的Smad，共过表达，恢复P19 CL 6 noggin分化为心肌细胞的能力，而稳定过表达的Smad 6，抑制性Smad，完全阻断P19 CL 6的分化，这表明Smad途径是必要的心肌细胞分化。ATF-2通过与Smad 1/4和TAK 1的协同作用激活βMHC启动子活性，促进P19 CL 6 noggin的终末心肌细胞分化;而过表达显性负性ATF-2则降低了几个心肌特异性基因的启动子活性，抑制P19 CL 6的分化。这些结果表明，Smads，TAK 1，和他们的共同目标ATF-2合作在心肌细胞分化中发挥关键作用。
We previously demonstrated that bone morphogenetic proteins (BMPs) induce cardiomyocyte differentiation through the mitogen-activated protein kinase kinase kinase TAK1. Transcription factors Smads mediate transforming growth factor-β signaling and the ATF/CREB family transcription factor ATF-2 has recently been shown to act as a common target of the Smad and the TAK1 pathways. We here examined the role of Smads and ATF-2 in cardiomyocyte differentiation of P19CL6, a clonal derivative of murine P19 cells. Although P19CL6 efficiently differentiates into cardiomyocytes when treated with dimethyl sulfoxide, P19CL6noggin, a P19CL6 cell line constitutively overexpressing the BMP antagonist noggin, did not differentiate into cardiomyocytes. Cooverexpression of Smad1, a ligand-specific Smad, and Smad4, a common Smad, restored the ability of P19CL6noggin to differentiate into cardiomyocytes, whereas stable overexpression of Smad6, an inhibitory Smad, completely blocked differentiation of P19CL6, suggesting that the Smad pathway is necessary for cardiomyocyte differentiation. ATF-2 stimulated the βMHC promoter activity by the synergistic manner with Smad1/4 and TAK1 and promoted terminal cardiomyocyte differentiation of P19CL6noggin, whereas overexpression of the dominant negative form of ATF-2 reduced the promoter activities of several cardiac-specific genes and inhibited differentiation of P19CL6. These results suggest that Smads, TAK1, and their common target ATF-2 cooperatively play a critical role in cardiomyocyte differentiation.
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影响因子：
64.8
作者：
Lagna, G;Hata, A;Massague, J
通讯作者：
Massague, J
影响因子：
64.8
作者：
Imamura, T;Takase, M;Miyazono, K
通讯作者：
Miyazono, K
DOI：
10.1073/pnas.88.9.3720
发表时间：
1991-05-01
影响因子：
11.1
作者：
HAI, T;CURRAN, T
通讯作者：
CURRAN, T
影响因子：
5.3
作者：
ARCECI, RJ;KING, AAJ;WILSON, DB
通讯作者：
WILSON, DB
影响因子：
2.5
作者：
HAN, Y;DENNIS, JE;FISCHMAN, DA
通讯作者：
FISCHMAN, DA