NF-κB activation upon interaction of HIV-1 envelope glycoproteins with cell surface CD4 involves IκB kinases
NF-κB activation upon interaction of HIV-1 envelope glycoproteins with cell surface CD4 involves IκB kinases
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DOI：
10.1016/s0014-5793(02)02566-8
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发表时间：
2002-04-10
期刊：
影响因子：
3.5
通讯作者：
Briant, L
中科院分区：
文献类型：
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作者：
Bossis, G;Salinas, S;Briant, L
人类免疫缺陷病毒1型包膜糖蛋白(gp120(Env))与细胞表面的CD4受体结合，触发一系列的细胞内效应，导致T细胞活化和细胞周期进入。在这些影响中，我们和其他人以前报道了核因子-kappaB(NF-kappaB)转录因子的核易位。本工作进一步研究了gp120(Env)诱导的核因子-kappaB活化的信号转导途径。我们证明gp120(Env)-CD4相互作用刺激IkappaB-α抑制蛋白的过度磷酸化。相反，过表达显性负的IkappaB-α转基因在S32和S36残基突变，取消gp120(Env)诱导的NF-kappaB激活。发现KKS活性在CD4与gp120(Env)结合后选择性地增强，并介导IkappaB-α的磷酸化，而显性-阴性形式的IKKS共转染实验抑制了gp120(Env)诱导的NF-kappaB的激活。综上所述，这些结果证实了IKKS复合体在gp120(Env)诱导的NF-kappaB活化中起关键作用。(C)2002年，由Elsevier Science B.V.代表欧洲生化学会联合会出版。
Human immunodeficiency virus type-1 envelope glycoprotein (gp120(env)) binding to cell surface CD4 receptor triggers a broad range of intracellular effects leading to T cell activation and cell cycle entry. Among these effects we and others previously reported on the nuclear translocation of the nuclear factor-kappaB (NF-kappaB) transcription factor. The present work further investigates the signal transduction pathways involved in gp120(env)-induced NF-kappaB activation. We demonstrate that gp120(env)-CD4 interaction stimulates the hyperphosphorylation of IkappaB-alpha inhibitory protein. Conversely, overexpression of a dominant-negative IkappaB-alpha transgene mutated at S32 and S36 residues, abolishes gp120(env)-induced NF-kappaB activation. IkappaB kinases (IKKs) activity was found to be selectively enhanced following CD4 engagement with gp120(env) and to mediate the phosphorylation of IkappaB-alpha while co-transfection experiments using dominant-negative forms of IKKs inhibited gp120(env)-induced NF-kappaB activation. Taken together, these results confirm that IKKs complex play a key role in gp120(env)-induced NF-kappaB activation. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.