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J Virol, July 1998, p. 6207-6214, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Protein Tyrosine Kinase p56lck Is Required for Triggering NF-kappa B Activation upon Interaction of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein gp120 with Cell Surface CD4

Laurence Briant,1 Véronique Robert-Hebmann,1 Claire Acquaviva,1 Annegret Pelchen-Matthews,2 Mark Marsh,2 and Christian Devaux1,*

Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CRBM-CNRS UPR 1086, Institut de Biologie, Montpellier, France,1 and Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom2

Received 10 December 1997/Accepted 8 April 1998

We have previously shown that NF-kappa B 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-kappa B 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 p56lck as a possible cellular intermediate in this signal transduction pathway. Using human cervical carcinoma HeLa cells stably expressing CD4, p56lck, or both molecules, we provide direct evidence that expression of CD4 and p56lck is required for HIV-1-induced NF-kappa B translocation. Moreover, the fact that HIV-1 stimulation did not induce nuclear translocation of NF-kappa B in cells expressing a mutant form of CD4 at position 420 (C420A) and the wild-type p56lck indicates the requirement for a functional CD4-p56lck complex.

* Corresponding author. Mailing address: Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CRBM-CNRS UPR 1086, 4 Boulevard Henri IV, 34060 Montpellier Cedex, France. Phone: (33)-4-67-60-86-60. Fax: (33)-4-67-60-44-20. E-mail: devaux{at}sc.univ-montp1.fr.

J Virol, July 1998, p. 6207-6214, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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