The protein tyrosine kinase p56lck is required for triggering NF-kappaB activation upon interaction of human immunodeficiency virus type 1 envelope glycoprotein gp120 with cell surface CD4.
We have previously shown that NF-kappaB nuclear translocation can be observed upon human immunodeficiency virus type 1 (HIV-1) binding to cells expressing the wild-type CD4 molecule, but not in cells expressing a truncated form of CD4 that lacks the cytoplasmic domain (M. Benkirane, K.-T. Jeang, and C. Devaux, EMBO J. 13:5559-5569, 1994). This result indicated that the signaling cascade which controls HIV-1-induced NF-kappaB activation requires the integrity of the CD4 cytoplasmic tail and suggested the involvement of a second protein that binds to this portion of the molecule. Here we investigate the putative role of p56(lck) as a possible cellular intermediate in this signal transduction pathway. Using human cervical carcinoma HeLa cells stably expressing CD4, p56(lck), or both molecules, we provide direct evidence that expression of CD4 and p56(lck) is required for HIV-1-induced NF-kappaB translocation. Moreover, the fact that HIV-1 stimulation did not induce nuclear translocation of NF-kappaB in cells expressing a mutant form of CD4 at position 420 (C420A) and the wild-type p56(lck) indicates the requirement for a functional CD4-p56(lck) complex.
Briant
L
L
Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CRBM-CNRS UPR 1086, Institut de Biologie, Montpellier, France.
Robert-Hebmann
V
V
Acquaviva
C
C
Pelchen-Matthews
A
A
Marsh
M
M
Devaux
C
C
D001692:Biological Transport; D015704:CD4 Antigens / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D016328:NF-kappa B; D010566:Virulence Factors, Bordetella; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019204:GTP-Binding Proteins