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Binding and activity of all human alpha interferon subtypes.

机译:所有人类α干扰素亚型的结合和活性。

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Vertebrates have multiple genes encoding Type I interferons (IFN), for reasons that are not fully understood. The Type I IFN appear to bind to the same heterodimeric receptor and the subtypes have been shown to have different potencies in various experimental systems. To put this concept on a quantitative basis, we have determined the binding affinities and rate constants of 12 human Alpha-IFN subtypes to isolated interferon receptor chains 1 and 2. Alpha-IFNs bind IFNAR1 and IFNAR2 at affinities of 0.5-5 muM and 0.4-5 nM respectively (except for IFN-alpha1 - 220 nM). Additionally we have examined the biological activity of these molecules in several antiviral and antiproliferative models. Particularly for antiproliferative potency, the binding affinity and activity correlate. However, the EC50 values differ significantly (1.5 nM versus 0.1 nM for IFN-alpha2 in WISH versus OVCAR cells). For antiviral potency, there are several instances where the relationship appears to be more complicated than simple binding. These results will serve as a point of reference for further understanding of this multiple ligand/receptor system.
机译:由于尚未完全了解的原因,脊椎动物具有编码I型干扰素(IFN)的多个基因。 I型IFN似乎结合相同的异二聚体受体,并且在各种实验系统中已显示出亚型具有不同的效力。为了定量地理解这一概念,我们确定了12种人Alpha-IFN亚型与分离的干扰素受体链1和2的结合亲和力和速率常数。Alpha-IFN以0.5-5μM和0.4的亲和力结合IFNAR1和IFNAR2。分别为-5 nM(IFN-α1-220nM除外)。此外,我们已经在几种抗病毒和抗增殖模型中检查了这些分子的生物学活性。特别是对于抗增殖能力,结合亲和力和活性相关。但是,EC50值存在显着差异(在WISH细胞与OVCAR细胞中,IFN-α2的EC50值分别为1.5 nM和0.1 nM)。对于抗病毒效力,在某些情况下关系似乎比简单的结合更为复杂。这些结果将作为进一步理解该多配体/受体系统的参考。

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