Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin
Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin
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DOI：
10.1128/mcb.14.6.3810-3821.1994
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发表时间：
1994-06
影响因子：
5.3
通讯作者：
J. Cárcamo;Frances M B Weis;F. Ventura;R. Wieser;J. Wrana;L. Attisano;J. Massagué
中科院分区：
文献类型：
--
作者：
J. Cárcamo;Frances M B Weis;F. Ventura;R. Wieser;J. Wrana;L. Attisano;J. Massagué
转化生长因子 β (TGF-β) 和激活素与受体复合物结合，该复合物含有两种关系较远的跨膜丝氨酸/苏氨酸激酶，称为 I 型和 II 型受体。 II 型受体决定配体结合特异性，并且每种受体都与 I 型受体的不同组成部分相互作用。在这里，我们鉴定了一种新的激活素 I 型受体 ActR-IB，其激酶结构域与最近克隆的 TGF-β I 型受体 T beta R-I 的激酶结构域几乎相同。 ActR-IB具有I型受体的结构和结合特性：它仅在存在II型激活素受体的情况下结合激活素，并与II型激活素受体形成异聚非共价复合物。在 Mv1Lu 肺上皮细胞中，ActR-IB 和 T beta R-I 发出与其相应配体和 II 型受体相关的一组常见的生长抑制和转录反应信号。转录反应包括纤连蛋白和纤溶酶原激活剂抑制剂 1 表达升高。尽管 T beta R-I 和 ActR-IB 的激酶结构域几乎相同（90% 氨基酸序列同一性），但它们相应的 II 型受体激酶结构域彼此非常不同（42% 氨基酸序列同一性）。因此，TGF-β 和激活素发出的一组特定反应的信号与其复合物中相似的 I 型激酶的存在相关。事实上，其他 TGF-β 和激活素 I 型受体（TSR-I 和 ActR-I）的激酶结构域与 T β R-I 和 ActR-IB 的激酶结构域明显不同，它们不能替代这些生长抑制和细胞外基质转录反应的介体。因此，我们得出结论，I 型受体亚基是 TGF-β 和激活素受体复合物发送的信号的主要指示符。
Transforming growth factor beta (TGF-beta) and activin bind to receptor complexes that contain two distantly related transmembrane serine/threonine kinases known as receptor types I and II. The type II receptors determine ligand binding specificity, and each interacts with a distinct repertoire of type I receptors. Here we identify a new type I receptor for activin, ActR-IB, whose kinase domain is nearly identical to that of the recently cloned TGF-beta type I receptor, T beta R-I. ActR-IB has the structural and binding properties of a type I receptor: it binds activin only in the presence of an activin type II receptor and forms a heteromeric noncovalent complex with activin type II receptors. In Mv1Lu lung epithelial cells, ActR-IB and T beta R-I signal a common set of growth-inhibitory and transcriptional responses in association with their corresponding ligands and type II receptors. The transcriptional responses include elevated expression of fibronectin and plasminogen activator inhibitor 1. Although T beta R-I and ActR-IB are nearly identical in their kinase domains (90% amino acid sequence identity), their corresponding type II receptor kinase domains are very different from each other (42% amino acid sequence identity). Therefore, signaling of a specific set of responses by TGF-beta and activin correlates with the presence of similar type I kinases in their complex. Indeed, other TGF-beta and activin type I receptors (TSR-I and ActR-I) whose kinase domains significantly diverge from those of T beta R-I and ActR-IB do not substitute as mediators of these growth-inhibitory and extracellular matrix transcriptional responses. Hence, we conclude that the type I receptor subunits are primary specifiers of signals sent by TGF-beta and activin receptor complexes.