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首页> 外文期刊>Molecular and Cellular Biology >Activin and inhibin have antagonistic effects on ligand-dependent heteromerization of the type I and type II activin receptors and human erythroid differentiation.
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Activin and inhibin have antagonistic effects on ligand-dependent heteromerization of the type I and type II activin receptors and human erythroid differentiation.

机译：激活素和抑制素对I型和II型激活素受体的配体依赖性异源化和人类红系分化具有拮抗作用。

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Activins and inhibins belong to the transforming growth factor beta (TGF-beta)-like superfamily and exert their effects on a broad range of cellular targets by modulating cell differentiation and proliferation. Members of this family interact with two structurally related classes of receptors (type I and type II), both containing a serine/threonine kinase domain. When expressed alone, the type II but not the type I activin receptor can bind activin. However, the presence of a type I receptor is required for signaling. For TGF-beta1, ligand binding to the type II receptor results in the recruitment and transphosphorylation of the type I receptor. Transient overexpression of the two types of activin receptor results in ligand-independent receptor heteromerization and activation. Nevertheless, activin addition to the transfected cells increased complex formation between the two receptors, suggesting a mechanism of action similar to that observed for the TGF-beta receptor. In the present study, we generated a stable cell line, overexpressing the two types of activin receptor upon induction, in the human erythroleukemia cell line K562. We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. Using this stable line, we analyzed the effects of activin and inhibin on human erythroid differentiation. Our results indicate that activin signal transduction mediated through its type I and type II receptors results in an increase in the hemoglobin content of the cells and limits their proliferation. Finally, using cell lines that can be induced to overexpress ActRII and ActRIB or ActRIB only, we show that the inhibin antagonistic effects on activin-induced biological responses are mediated through a competition for the type II activin receptor but also require the presence of an inhibin-specific binding component.
机译：激活素和抑制素属于转化生长因子β（TGF-β）样超家族，并通过调节细胞分化和增殖而对多种细胞靶标发挥作用。该家族的成员与两种结构相关的受体（I型和II型）相互作用，它们均含有丝氨酸/苏氨酸激酶结构域。当单独表达时，II型激活素受体而不是I型激活素受体可以结合激活素。然而，I型受体的存在是信号传导所必需的。对于TGF-beta1，配体与II型受体的结合导致I型受体的募集和转磷酸化。两种激活素受体的瞬时过表达导致不依赖配体的受体异源化和激活。尽管如此，激活素除了被转染的细胞外，还增加了两个受体之间的复合物形成，表明其作用机理与TGF-β受体相似。在本研究中，我们在人红白血病细胞系K562中产生了一种稳定的细胞系，在诱导后过表达两种激活素受体。我们在这里证明激活素以时间依赖性方式特异性诱导I型和II型受体之间的异源单体形成。使用此稳定线，我们分析了激活素和抑制素对人红系分化的影响。我们的结果表明，通过其I型和II型受体介导的激活素信号转导导致细胞血红蛋白含量的增加，并限制了它们的增殖。最后，使用可以被诱导过表达ActRII和ActRIB或仅ActRIB的细胞系，我们表明对激活素诱导的生物反应的抑制素拮抗作用是通过竞争II型激活素受体而介导的，但也需要存在抑制素特定的绑定组件。

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