The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/11/1793/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 10, November 17, 1997 1793-1798

Brief Definitive Reports

Signal Transduction Due to HIV-1 Envelope Interactions with Chemokine Receptors CXCR4 or CCR5

Craig B. Davis*, Ivan Dikic§, Derya Unutmaz*,{ddagger}, C. Mark Hill*, James Arthos||, Michael A. Siani, Darren A. Thompson, Joseph Schlessinger§, and Dan R. Littman*,{ddagger}

From the * Division of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, {ddagger} Howard Hughes Medical Institute, and § Department of Pharmacology, New York University Medical Center, New York 10016; || National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892; and Gryphon Sciences, South San Francisco, California 94080

Infection with HIV-1 requires expression of CD4 and the chemokine receptors CXCR4 or CCR5 at the target cell surface. Engagement of these receptors by the HIV-1 envelope glycoprotein is essential for membrane fusion, but may additionally activate intracellular signaling pathways. In this study, we demonstrate that chemokines and HIV-1 envelope glycoproteins from both T-tropic and macrophage-tropic strains rapidly induce tyrosine phosphorylation of the protein tyrosine kinase Pyk2. The response requires CXCR4 and CCR5 to be accessible on the cell surface. The results presented here provide the first evidence for activation of an intracellular signaling event that can initiate multiple signaling pathways as a consequence of contact between HIV-1 and chemokine receptors.

Address correspondence to Craig B. Davis, Skirball Institute for Biomolecular Medicine, 2-17, NYU Medical Center, 540 First Ave, New York, NY 10016. Phone: 212-263-6921; FAX: 212-263-5711; E-mail: davis{at}saturn.med.nyu.edu—I. Dikic's present address is Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, Husargatan 3, Box 595, S-75124 Uppsala, Sweden.

D.R. Littman is an Investigator of the Howard Hughes Medical Institute. This work was supported by grants from the National Institutes of Health (D.R. Littman) and Sugen, Inc. (J. Schlessinger).

C.B. Davis and I. Dikic contributed equally to this study.


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