Signals transduced through the CD4 molecule on T lymphocytes activate NF-kappa B.
We have demonstrated that native envelope glycoproteins of HIV-1, gp160 can induce activation of the transcription factor, NF-kappa B. The stimulatory effects of gp160 are mediated through the CD4 molecule, since pretreatment with soluble CD4 abrogates its activity. The gp160-induced NF-kappa B complex consists of p65, p50 and c-rel proteins. The stimulatory effect of gp160 on NF-kappa B activation is protein synthesis independent, is dependent upon protein tyrosine phosphorylation, and abrogated by inhibitors of protein kinase C. The gp160-mediated activation of NF-kappa B in CD4 positive T cells may be involved in biological effects, e.g., enhanced HIV replication, hypergammaglobulinemia, increased cytokine secretion, hypercellularity in bone marrow and apoptosis.
Chirmule
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Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030.
Kalyanaraman
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VS
Pahwa
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S
D015703:Antigens, CD / Q000502:physiology*; D015704:CD4 Antigens / Q000187:drug effects / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D015686:Gene Products, env / Q000494:pharmacology*; D006678:HIV / Q000276:immunology; D019302:HIV Envelope Protein gp160; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011498:Protein Precursors / Q000494:pharmacology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D015704:CD4 Antigens; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D016328:NF-kappa B; D011498:Protein Precursors