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首页> 外文期刊>Journal of Cellular Physiology >Intracellular dynamics of Smad-mediated TGFbeta signaling.
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Intracellular dynamics of Smad-mediated TGFbeta signaling.

机译：细胞内动态Smad-mediated TGFbeta信号。

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The transforming growth factor-beta (TGFbeta) family represents a class of signaling molecules that plays a central role in morphogenesis, growth, and cell differentiation during normal embryonic development. Members of this growth factor family are particularly vital to development of the mammalian secondary palate where they regulate palate mesenchymal cell proliferation and extracellular matrix synthesis. Such regulation is particularly critical since perturbation of either cellular process results in a cleft of the palate. While the cellular and phenotypic effects of TGFbeta on embryonic craniofacial tissue have been extensively catalogued, the specific genes that function as downstream mediators of TGFbeta action in the embryo during palatal ontogenesis are poorly defined. Embryonic palatal tissue in vivo and murine embryonic palate mesenchymal (MEPM) cells in vitro secrete and respond to TGFbeta. In the current study, elements of the Smad component of the TGFbeta intracellular signaling system were identified and characterized in cells of the embryonic palate and functional activation of the Smad pathway by TGFbeta1, TGFbeta2, and TGFbeta3 was demonstrated. TGFbeta-initiated Smad signaling in cells of the embryonic palate was found to result in: (1) phosphorylation of Smad 2; (2) nuclear translocation of the Smads 2, 3, and 4 protein complex; (3) binding of Smads 3 and 4 to a consensus Smad binding element (SBE) oligonucleotide; (4) transactivation of transfected reporter constructs, containing TGFbeta-inducible Smad response elements; and (4) increased expression of gelatinases A and B (endogenous genes containing Smad response elements) whose expression is critical to matrix remodeling during palatal ontogenesis. Collectively, these data point to the presence of a functional Smad-mediated TGFbeta signaling system in cells of the developing murine palate. J. Cell. Physiol. 197: 261-271, 2003. Copyright 2003 Wiley-Liss, Inc.
机译：转化生长因子(TGFbeta)家庭代表一类信号分子在形态发生中起着核心作用,在正常增长,细胞分化胚胎发育。家庭因素尤其重要哺乳动物的发展二级口感它们调节口感间充质细胞在哪里增殖和细胞外基质的合成。这种监管尤为重要扰动的细胞过程的结果裂的口味。表型TGFbeta对胚胎的影响颅面组织广泛编目,特定的基因功能下游TGFbeta行动的介质胚胎腭个体发育期间不佳定义的。小鼠胚胎腭间充质细胞(MEPM)体外分泌TGFbeta并作出反应。目前的研究中,Smad组成部分的元素TGFbeta胞内信号系统识别和细胞的特点胚胎口感和功能的激活短信TGFbeta1偏pathway, TGFbeta2和TGFbeta3是证明。信号在细胞胚胎的口感,结果发现:(1)Smad磷酸化2;和4蛋白质复杂;4共识Smad绑定元素(”寡核苷酸;转染记者构造,包含TGFbeta-inducible Smad响应元素;明胶酶A和B的表达增加(内源性基因包含Smad响应矩阵元素)的表达是至关重要的重建腭个体发育期间。总的来说,这些数据点的存在一个功能Smad-mediated TGFbeta信号系统在细胞发展中小鼠的口味。j .细胞。2003 Wiley-Liss, Inc。

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