Determinants of specificity in TGF-β signal transduction
Determinants of specificity in TGF-β signal transduction
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DOI：
10.1101/gad.12.14.2144
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发表时间：
1998-07-15
影响因子：
10.5
通讯作者：
Massagué, J
中科院分区：
文献类型：
--
作者：
Chen, YG;Hata, A;Massagué, J
TGF-β家族的信号转导涉及一系列受体丝氨酸/苏氨酸激酶、作为受体底物的Smad蛋白和靶向特定基因的Smad相关转录因子。我们已经确定了决定受体和Smads之间以及Smads和TGF-β和BMP途径中的转录因子之间的选择性相互作用的离散结构元件。I型受体激酶结构域的L45环中的一组四个残基和Smad羧基末端结构域的L3环中的一组匹配的两个残基建立了受体-Smad相互作用的特异性。Smad羧基末端结构域高度暴露的α-螺旋2中的一簇残基指定与DNA结合因子Fast 1的相互作用，并因此指定由该途径介导的基因应答。通过建立特定的相互作用，这些决定因素保持TGF-β和BMP途径彼此分离。
Signal transduction by the TGF-beta family involves sets of receptor serine/threonine kinases, Smad proteins that act as receptor substrates, and Smad-associated transcription factors that target specific genes. We have identified discrete structural elements that dictate the selective interactions between receptors and Smads and between Smads and transcription factors in the TGF-beta and BMP pathways. A cluster of four residues in the L45 loop of the type I receptor kinase domain, and a matching set of two residues in the L3 loop of the Smad carboxy-terminal domain establish the specificity of receptor-Smad interactions. A cluster of residues in the highly exposed alpha-helix 2 of the Smad carboxy-terminal domain specify the interaction with the DNA-binding factor Fast1 and, as a result, the gene responses mediated by the pathway. By establishing specific interactions, these determinants keep the TGF-beta and BMP pathways segregated from each other.