Hu Fang, Nicholas John
SKCCC at Johns Hopkins, 1650 Orleans Street, Room 309, Baltimore, MD 21231, USA.
J Virol. 2006 Nov;80(21):10874-8. doi: 10.1128/JVI.00767-06. Epub 2006 Sep 6.
Human herpesvirus 8 (HHV-8) viral interleukin-6 (vIL-6) mediates signaling through the gp130 signal transducer but unlike human IL-6 (hIL-6) does not require the nonsignaling gp80 alpha subunit of the IL-6 receptor complex. By utilizing a gp80-refractory vIL-6 variant, vIL-6(R189L), we found that signal transduction, as measured by STAT1 and STAT3 activation and gp130 tyrosine phosphorylation in gp80+/gp130+ HEK293T cells, was modulated by gp80. Furthermore, the signaling and BAF-130 cell growth-promoting activities of vIL-6 and hIL-6 could be distinguished, and exogenous addition of soluble gp80 enhanced cell growth supported by vIL-6. Our findings demonstrate that gp80 can modulate vIL-6 activity and that vIL-6 and hIL-6 signaling are not directly equivalent.
人类疱疹病毒8型(HHV - 8)的病毒白细胞介素-6(vIL - 6)通过gp130信号转导子介导信号传导,但与人类白细胞介素-6(hIL - 6)不同的是,它不需要白细胞介素-6受体复合物的无信号传导功能的gp80α亚基。通过利用一种对gp80不敏感的vIL - 6变体vIL - 6(R189L),我们发现在gp80+/gp130+的HEK293T细胞中,通过STAT1和STAT3激活以及gp130酪氨酸磷酸化来衡量的信号转导受到gp80的调节。此外,vIL - 6和hIL - 6的信号传导及BAF - 130细胞生长促进活性能够被区分,并且可溶性gp80的外源添加增强了vIL - 6所支持的细胞生长。我们的研究结果表明,gp80可以调节vIL - 6的活性,并且vIL - 6和hIL - 6的信号传导并非直接等同。