Itoh Susumu, ten Dijke Peter
Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Curr Opin Cell Biol. 2007 Apr;19(2):176-84. doi: 10.1016/j.ceb.2007.02.015. Epub 2007 Feb 20.
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.
转化生长因子-β（TGF-β）家族成员是高度保守的多功能细胞间信号蛋白，对控制胚胎发育和组织稳态至关重要。乍一看，通过TGF-β家族成员进行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，这些受体激活细胞内的Smad效应蛋白，而Smad效应蛋白又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，TGF-β/Smad信号通路的每一步都存在额外的复杂性。TGF-β信号成分的表达、激活与失活、亚细胞定位和稳定性受到严格调控，并受到其他信号通路的影响。现已鉴定出大量与Smad相互作用的蛋白以及Smad的多种翻译后修饰。最近，我们在理解TGF-β家族信号如何减弱和终止以维持对这一多功能信号通路的控制方面取得了重要进展。
