HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4+ T cells

被引：111

作者：

Cicala, C ^{[1
]}

Arthos, J ^{[1
]}

Rubbert, A ^{[1
]}

Selig, S ^{[1
]}

Wildt, K ^{[1
]}

Cohen, OJ ^{[1
]}

Fauci, AS ^{[1
]}

机构：

[1] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2000年 / 97卷 / 03期

关键词：

D O I：

10.1073/pnas.97.3.1178

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Binding of HIV type 1 (HIV-l) envelope glycoproteins to the surface of a CD4(+) T cell transduces intracellular signals through the primary envelope receptor, CD4, and a coreceptor, either CCR5 or CXCR4. Furthermore, envelope-CD4(+) cell interactions increase rates of apoptosis in peripheral blood mononuclear cells (PBMCs). We demonstrate that in primary T lymphocytes. recombinant HIV-1 envelope proteins induce the activation of caspase-3 and caspase-6, which belong to a family of cysteine proteases that, upon activation, promote programmed cell death. Envelope-mediated activation of caspase-3 and caspase-6 depended on envelope-CD4 receptor interactions; CCR5-utilizing as well as CXCR4-utilizing envelopes elicited this response. Focal adhesion kinase (FAK) is a substrate of both caspase-3 and caspase-6, and inactivation of FAK by these caspases promotes apoptosis, Envelope treatment of lymphocytes led to the cleavage of FAK in a manner consistent with caspase-mediated cleavage.

引用

页码：1178 / 1183

页数：6

共 66 条

[1] Differential susceptibility to HIV-GP120-sensitized apoptosis in CD4(+) T-cell clones with different T-helper phenotypes: Role of CD95/CD95L interactions [J].