Cárcamo J, Weis F M, Ventura F, Wieser R, Wrana J L, Attisano L, Massagué J
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Mol Cell Biol. 1994 Jun;14(6):3810-21. doi: 10.1128/mcb.14.6.3810-3821.1994.
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.
转化生长因子β（TGF-β）和激活素与受体复合物结合，该复合物包含两种远亲的跨膜丝氨酸/苏氨酸激酶，即I型和II型受体。II型受体决定配体结合特异性，且每种II型受体都与不同的I型受体组合相互作用。在此，我们鉴定出一种新的激活素I型受体ActR-IB，其激酶结构域与最近克隆的TGF-βI型受体TβR-I几乎相同。ActR-IB具有I型受体的结构和结合特性：它仅在激活素II型受体存在的情况下结合激活素，并与激活素II型受体形成异源非共价复合物。在Mv1Lu肺上皮细胞中，ActR-IB和TβR-I与其相应的配体和II型受体一起，引发一组共同的生长抑制和转录反应。转录反应包括纤连蛋白和纤溶酶原激活物抑制剂1的表达升高。尽管TβR-I和ActR-IB的激酶结构域几乎相同（氨基酸序列同一性为90%），但它们相应的II型受体激酶结构域彼此差异很大（氨基酸序列同一性为42%）。因此，TGF-β和激活素引发的一组特定反应的信号传导与其复合物中相似的I型激酶的存在相关。实际上，其他TGF-β和激活素I型受体（TSR-I和ActR-I），其激酶结构域与TβR-I和ActR-IB的激酶结构域有显著差异，不能替代作为这些生长抑制和细胞外基质转录反应的介质。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出信号的主要决定因素。
