HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4+ T cells
C Cicala, J Arthos, A Rubbert, S Selig… - Proceedings of the …, 2000 - National Acad Sciences
C Cicala, J Arthos, A Rubbert, S Selig, K Wildt, OJ Cohen, AS Fauci
Proceedings of the National Academy of Sciences, 2000•National Acad SciencesBinding of HIV type 1 (HIV-1) 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 …
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 …
Binding of HIV type 1 (HIV-1) 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.
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