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.