Activins are one of the three distinct subclasses within the greater Transforming growth factor β (TGFβ) superfamily. First discovered for their critical roles in reproductive biology, activins have since been shown to alter cellular differentiation and proliferation. At present, members of the activin subclass include activin A (ActA), ActB, ActC, ActE, and the more distant members myostatin and GDF11. While the biological roles and signaling mechanisms of most activins class members have been well-studied, the signaling potential of ActE has remained largely unknown. Here, we characterized the signaling capacity of homodimeric ActE. Molecular modeling of the ligand:receptor complexes showed that ActC and ActE shared high similarity in both the type I and type II receptor binding epitopes. ActE signaled specifically through ALK7, utilized the canonical activin type II receptors, ActRIIA and ActRIIB, and was resistant to the extracellular antagonists follistatin and WFIKKN. In mature murine adipocytes, ActE invoked a SMAD2/3 response via ALK7, like ActC. Collectively, our results establish ActE as a specific signaling ligand which activates the type I receptor, ALK7.

中文翻译：

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激活素 E 是一种转化生长因子 β 配体，通过激活素受体样激酶 7 特异性发出信号

激活素是转化生长因子 β (TGFβ) 超家族中的三个不同亚类之一。激活素最初因其在生殖生物学中的关键作用而被发现，后来被证明可以改变细胞分化和增殖。目前，激活素亚类的成员包括激活素A (ActA)、ActB、ActC、ActE，以及更远的成员肌​​生长抑制素和GDF11。虽然大多数激活素类成员的生物学作用和信号传导机制已得到充分研究，但 ActE 的信号传导潜力仍然很大程度上未知。在这里，我们表征了同二聚体 ActE 的信号传导能力。配体：受体复合物的分子模型表明，ActC 和 ActE 在 I 型和 II 型受体结合表位方面具有高度相似性。 ActE 通过 ALK7 特异性发出信号，利用经典的激活素 II 型受体 ActRIIA 和 ActRIIB，并且对细胞外拮抗剂卵泡抑素和 WFIKKN 具有抗性。在成熟的小鼠脂肪细胞中，ActE 与 ActC 一样，通过 ALK7 引发 SMAD2/3 反应。总的来说，我们的结果表明 ActE 是一种特异性信号配体，可激活 I 型受体 ALK7。