THE PROTEIN-TYROSINE KINASE P56(LCK) IS REQUIRED FOR TRIGGERING NF-KAPPA-B ACTIVATION UPON INTERACTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN GP120 WITH CELL-SURFACE CD4

We have previously shown that NF-kappa B nuclear translocation can be observed upon human immunodeficiency virus type 1 (HIV-1) binding to c ells expressing the wild-type CD4 molecule, but not in cells expressin g a truncated form of CD4 that lacks the cytoplasmic domain (M. Benkir ane, K.-T, Jeang, and C. Devaux, EMBO J. 13:5559-5569, 1994). This res ult indicated that the signaling cascade which controls HTV-1-induced NF-KB activation requires the integrity of the CD4 cytoplasmic tail an d suggested the involvement of a second protein that binds to this por tion of the molecule. Here we investigate the putative role of p56(lck ) as a possible cellular intermediate in this signal transduction path way. Using human cervical carcinoma HeLa cells stably expressing CD4, p56(lck), or both molecules, we provide direct evidence that expressio n of CD4 and p56(lck) is required for HIV-1-induced NF-kappa B translo cation, Moreover, the fact that HIV-1 stimulation did not induce nucle ar translocation of NF-kappa B in cells expressing a mutant form of CD 4 at position 420 (C420A) and the wild-type p56(lck)indicates the requ irement for a functional CD4-p56(lck) complex.