N-linked glycosylation is required for optimal function of Kaposi's sarcoma herpesvirus-encoded, but not cellular, interleukin 6.

N-linked glycosylation is required for optimal function of Kaposi's sarcoma herpesvirus-encoded, but not cellular, interleukin 6.
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DOI:
10.1084/jem.20031205
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发表时间:
2004-02-16
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Miller G
Miller G
中科院分区:
其他
文献类型:
--
作者:
Dela Cruz CS;Lee Y;Viswanathan SR;El-Guindy AS;Gerlach J;Nikiforow S;Shedd D;Gradoville L;Miller G

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卡波西肉瘤相关疱疹病毒白介素6(VIL-6)是人类细胞因子IL-6(hIL-6)的结构和功能同源物。IL-6和VIL-6具有相似的生物学功能,它们都通过gp130受体亚基激活Janus酪氨酸激酶(JAK)1和信号转导和转录激活因子(STAT)1/3通路。在这里,我们证明了VIL-6在N78和N89是N连接的糖基化的,并证明了VIL-6的N89位的N连接的糖基化显著地增强了与gp130的结合,通过JAK1-STAT1/3途径传递信号,并在细胞因子依赖的细胞增殖生物测定中发挥作用。虽然IL-6在N73位也是N-糖基化的,并且是O-糖基化的,但对于IL-6受体α依赖的gp130结合或通过JAK1-STAT1/3信号转导,非糖基化的hIL-6和糖基化的hIL-6在刺激B细胞增殖方面不同。这些发现突出了N-连接糖基化在病毒和细胞IL-6中的不同功能作用。
Kaposi's sarcoma–associated herpesvirus interleukin-6 (vIL-6) is a structural and functional homologue of the human cytokine IL-6 (hIL-6). hIL-6 and vIL-6 exhibit similar biological functions and both act via the gp130 receptor subunit to activate the Janus tyrosine kinase (JAK)1 and signal transducer and activator of transcription (STAT)1/3 pathway. Here we show that vIL-6 is N-linked glycosylated at N78 and N89 and demonstrate that N-linked glycosylation at site N89 of vIL-6 markedly enhances binding to gp130, signaling through the JAK1-STAT1/3 pathway and functions in a cytokine-dependent cell proliferation bioassay. Although hIL-6 is also N-glycosylated at N73 and multiply O-glycosylated, neither N-linked nor O-linked glycosylation is necessary for IL-6 receptor α–dependent binding to gp130 or signaling through JAK1-STAT1/3. As distinct from vIL-6, unglycosylated hIL-6 is as potent as glycosylated hIL-6 in stimulating B cell proliferation. These findings highlight distinct functional roles of N-linked glycosylation in viral and cellular IL-6.
DOI: 10.1016/1043-4666(93)90039-8
发表时间: 1993-09-01
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