Activation of the PAK-related kinase by human immunodeficiency virus type 1 Nef in primary human peripheral blood lymphocytes and macrophages leads to phosphorylation of a PIX-p95 complex

被引:40
作者
Brown, A
Wang, X
Sawai, E
Cheng-Mayer, C
机构
[1] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
[2] Univ Calif Davis, Davis, CA 95616 USA
关键词
D O I
10.1128/JVI.73.12.9899-9907.1999
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Human immunodeficiency virus type 1 (HIV-1) Nef enhances virus replication in both primary T lymphocytes and monocyte derived macrophages. This enhancement phenotype has been linked to the ability of Nef to modulate the activity of cellular kinases. We find that despite the reported high-affinity interaction between Nef and the Src kinase Hck in vitro, a Nef-Hck interaction in the context of HN-l-infected primary macrophages is not detectable. However, Nef binding and activation of the PAK-related kinase and phosphorylation of its substrate could be readily detected in both infected primary T lymphocytes and macrophages. Furthermore, we show that this substrate is a complex composed of the recently characterized PAK interacting partner PIX (PAK-interacting guanine nucleotide exchange factor) and its tightly associated p95 protein. PAK and PIX-p95 appear to be differentially activated and phosphorylated depending on the intracellular environment in which nef is expressed. These results identify the PLY-p95 complex as a novel effector of Nef in primary cells and suggest that the regulation of the PAK signaling pathway may differ in T cells and macrophages.
引用
收藏
页码:9899 / 9907
页数:9
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