Transforming growth factor (TGF-beta)-specific signaling by chimeric TGF-beta type II receptor with intracellular domain of activin type IIB receptor
Transforming growth factor (TGF-beta)-specific signaling by chimeric TGF-beta type II receptor with intracellular domain of activin type IIB receptor
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DOI：
10.1074/jbc.272.34.21187
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发表时间：
1997-08-22
影响因子：
4.8
通讯作者：
Heldin, CH
中科院分区：
文献类型：
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作者：
Persson, U;Souchelnytskyi, S;Heldin, CH
转化生长因子-β超家族的成员通过两个依次作用的丝氨酸/苏氨酸激酶受体，即I型和II型受体的不同异构体复合体来传递信号。我们产生了两种不同的嵌合超家族受体，即TβR-I/BMPR-IB和TβR-II/ACTR-IIB，TβR-I/BMPR-IB含有转化生长因子-βI型受体的胞外区(TPR-I)和骨形态发生蛋白IB的胞内区(BMPR-IB)。含有转化生长因子-βII受体胞外区(TPR-II)和激活素IIB受体胞内区(ACTR-IIB)的TβR-II/ACTR-IIB分别与野生型TPR-II和野生型TPR-I形成异构体复合体，稳定地转染水貂肺上皮细胞系，结果表明，TβR-II/ACTR-IIB在转化缺乏功能TPR-II的突变细胞系中，在转录信号的激活、细胞外基质的形成、生长抑制、生长抑制等方面恢复了对转录信号的激活、细胞外基质的形成、生长抑制、生长抑制的反应性和Smad磷酸化。此外，TβR-I/BMPR-IB和TβR-II/ACTR-IIB形成了一个响应于转化生长因子-β并诱导Smad1磷酸化的功能复合体，然而，复合体的形成不足以促进信号的传播，这表现在TβR-I/BMPR-IB不能在功能缺失的TPR-I的细胞系中恢复对转化生长因子-β的反应，转化生长因子-β1诱导的TβR-II/ACTR-IIB和TPR-I之间的复合体刺激内源性Smad2的磷酸化，一种类似转化生长因子的反应，与目前的受体激活模型一致，在该模型中，I型受体决定信号特异性。
Members of the transforming growth factor-beta (TGF-beta) superfamily signal via different heteromeric complexes of two sequentially acting serine/threonine kinase receptors, i,e, type I and type II receptors, We generated two different chimeric TGF-beta superfamily receptors, i.e. T beta R-I/BMPR-IB, containing the extracellular domain of TGF-beta type I receptor (TPR-I) and the intracellular domain of bone morphogenetic protein type IB receptor (BMPR-IB), and T beta R-II/ActR-IIB, containing the extracellular domain of TGF-beta type II receptor (TPR-II) and the intracellular domain of activin type IIB receptor (ActR-IIB), In the presence of TGF-beta 1, T beta R-I/BMPR-IB and T beta R-II/ActR-IIB formed heteromeric complexes with wild-type TPR-II and TPR-I, respectively, upon stable transfection in mink lung epithelial cell lines, We show that T beta R-II/ActR-IIB restored the responsiveness upon transfection in mutant cell lines lacking functional TPR II with respect to TGF-beta-mediated activation of a transcriptional signal, extracellular matrix formation, growth inhibition, and Smad phosphorylation. Moreover, T beta R-I/BMPR-IB and T beta R-II/ActR-IIB formed a functional complex in response to TGF-beta and induced phosphorylation of Smad1, However, complex formation is not enough for signal propagation, which is shown by the inability of T beta R-I/BMPR-IB to restore responsive ness to TGF-beta in cell lines deficient in functional TPR-I, The fact that the TGF-beta 1-induced complex between T beta R-II/ActR-IIB and TPR-I stimulated endogenous Smad2 phosphorylation, a TGF-beta-like response, is in agreement with the current model for receptor activation in which the type I receptor determines signal specificity.