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首页> 外文期刊>Molecular and Cellular Biology >The Tumor Necrosis Factor Receptor Stalk Regions Define Responsiveness to Soluble versus Membrane-Bound Ligand
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The Tumor Necrosis Factor Receptor Stalk Regions Define Responsiveness to Soluble versus Membrane-Bound Ligand

机译：肿瘤坏死因子受体茎区域定义对可溶性与膜结合配体的响应。

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The family of tumor necrosis factor receptors (TNFRs) and their ligands form a regulatory signaling network that controls immune responses. Various members of this receptor family respond differently to the soluble and membrane-bound forms of their respective ligands. However, the determining factors and underlying molecular mechanisms of this diversity are not yet understood. Using an established system of chimeric TNFRs and novel ligand variants mimicking the bioactivity of membrane-bound TNF (mTNF), we demonstrate that the membrane-proximal extracellular stalk regions of TNFR1 and TNFR2 are crucial in controlling responsiveness to soluble TNF (sTNF). We show that the stalk region of TNFR2, in contrast to the corresponding part of TNFR1, efficiently inhibits both the receptor's enrichment/clustering in particular cell membrane regions and ligand-independent homotypic receptor preassembly, thereby preventing sTNF-induced, but not mTNF-induced, signaling. Thus, the stalk regions of the two TNFRs not only have implications for additional TNFR family members, but also provide potential targets for therapeutic intervention.
机译：肿瘤坏死因子受体（TNFR）家族及其配体形成控制免疫应答的调节信号网络。该受体家族的各种成员对它们各自配体的可溶性和膜结合形式的反应不同。但是，这种多样性的决定因素和潜在的分子机制尚不清楚。使用已建立的嵌合TNFR和模拟膜结合TNF（mTNF）的生物活性的新型配体变体的系统，我们证明TNFR1和TNFR2的膜近端细胞外茎区域在控制对可溶性TNF（sTNF）的反应性中至关重要。我们显示，与TNFR1的相应部分相比，TNFR2的茎区域有效地抑制了受体在特定细胞膜区域的富集/聚簇和配体独立的同型受体预组装，从而阻止了sTNF诱导，而不是mTNF诱导，信号。因此，两个TNFR的茎区域不仅对额外的TNFR家族成员有影响，而且还提供了治疗干预的潜在靶标。

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