Negative regulation of TGF-β receptor/Smad signal transduction
Negative regulation of TGF-β receptor/Smad signal transduction
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DOI：
10.1016/j.ceb.2007.02.015
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发表时间：
2007-04-01
影响因子：
7.5
通讯作者：
ten Dijke, Peter
中科院分区：
文献类型：
--
作者：
Itoh, Susumu;ten Dijke, Peter
转化生长因子-β（TGF-β）家族的成员是高度保守的多功能细胞-细胞信号传导蛋白，其对于控制胚胎发生和组织稳态至关重要。乍一看，通过TGF-β家族成员的信号传导似乎是一个简单的过程：配体与特定的丝氨酸/苏氨酸激酶跨膜受体结合，激活细胞内的Smad效应蛋白，进而将信号传递到细胞核以控制基因转录。然而，最近的研究表明，在TGF-β/Smad通路的每一步都存在额外的复杂性。TGF-β信号传导组分的表达、活化和失活、亚细胞定位和稳定性受到严格调控，并受到来自其他信号传导途径的输入。已经确定了一系列广泛的Smad相互作用的合作伙伴和不同的翻译后修饰的Smad。最近，我们对TGF-β家族信号如何被减弱和终止以维持对这种多功能途径的控制的理解取得了重要进展。
Members of the transforming growth factor-beta (TGF-beta) family are highly conserved multifunctional cell-cell signaling proteins that are of key importance for controlling embryogenesis and tissue homeostasis. At first glance, signaling through TGF-beta family members appears to be a simple process: ligands bind to specific serine/threonine kinase transmembrane receptors, which activate intracellular Smad effector proteins, which in turn relay the signal to the nucleus to control gene transcription. However, recent research has revealed that additional layers of complexity exist at each step in the TGF-beta/Smad pathway. The expression, activation and inactivation, subcellular localization, and stability of TGF-beta signaling components are tightly regulated and subject to input from other signaling pathways. A broad array of Smad interacting partners and diverse post-translational modifications of Smads have been identified. Recently, important advances have been made in our understanding of how TGF-beta family signals are attenuated and terminated to maintain control over this versatile pathway.