title: Signal transduction due to HIV-1 envelope interactions with chemokine receptors CXCR4 or CCR5.
abstract: 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.
authors.affiliation: Division of Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, NYU Medical Center 10016, USA. davis@saturn.med.nyu.edu
authors.forename: C B
authors.initials: CB
authors.lastname: Davis
authors.forename: I
authors.initials: I
authors.lastname: Dikic
authors.forename: D
authors.initials: D
authors.lastname: Unutmaz
authors.forename: C M
authors.initials: CM
authors.lastname: Hill
authors.forename: J
authors.initials: J
authors.lastname: Arthos
authors.forename: M A
authors.initials: MA
authors.lastname: Siani
authors.forename: D A
authors.initials: DA
authors.lastname: Thompson
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
authors.forename: D R
authors.initials: DR
authors.lastname: Littman
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D051418:Focal Adhesion Kinase 2; D015686:Gene Products, env / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism / Q000494:pharmacology; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019713:Receptors, CCR5 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; D002118:Calcium