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J Virol, July 1998, p. 6207-6214, Vol. 72, No. 7
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-
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-
B Activation upon Interaction of Human
Immunodeficiency Virus Type 1 Envelope Glycoprotein gp120 with Cell
Surface CD4
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-
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-
B translocation. Moreover, the fact
that HIV-1 stimulation did not induce nuclear translocation of NF-
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.
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