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.
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17 November 1997
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Brief Definitive Report|
November 17 1997
Signal Transduction Due to HIV-1 Envelope Interactions with Chemokine Receptors CXCR4 or CCR5
Craig B. Davis,
Craig B. Davis
From the *Division of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, ‡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
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Ivan Dikic,
Ivan Dikic
From the *Division of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, ‡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
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Derya Unutmaz,
Derya Unutmaz
From the *Division of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, ‡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
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C. Mark Hill,
C. Mark Hill
From the *Division of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, ‡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
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James Arthos,
James Arthos
From the *Division of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, ‡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
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Michael A. Siani,
Michael A. Siani
From the *Division of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, ‡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
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Darren A. Thompson,
Darren A. Thompson
From the *Division of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, ‡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
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Joseph Schlessinger,
Joseph Schlessinger
From the *Division of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, ‡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
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Dan R. Littman
Dan R. Littman
From the *Division of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, ‡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
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Craig B. Davis
,
Ivan Dikic
,
Derya Unutmaz
,
C. Mark Hill
,
James Arthos
,
Michael A. Siani
,
Darren A. Thompson
,
Joseph Schlessinger
,
Dan R. Littman
From the *Division of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, ‡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
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: [email protected]—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.
Received:
July 25 1997
Revision Received:
September 15 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 186 (10): 1793–1798.
Article history
Received:
July 25 1997
Revision Received:
September 15 1997
Citation
Craig B. Davis, Ivan Dikic, Derya Unutmaz, C. Mark Hill, James Arthos, Michael A. Siani, Darren A. Thompson, Joseph Schlessinger, Dan R. Littman; Signal Transduction Due to HIV-1 Envelope Interactions with Chemokine Receptors CXCR4 or CCR5 . J Exp Med 17 November 1997; 186 (10): 1793–1798. doi: https://doi.org/10.1084/jem.186.10.1793
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