Blood, 2011-06, Vol.117 (24), p.6589-6599
2011
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Details
- Autor(en) / Beteiligte
- Titel
- DCIR-mediated enhancement of HIV-1 infection requires the ITIM-associated signal transduction pathway
- Ist Teil von
- Blood, 2011-06, Vol.117 (24), p.6589-6599
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2011
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor expressed at high levels on dendritic cells (DCs). This surface molecule acts as an attachment factor for HIV-1 on DCs and contributes to trans- and cis-infection pathways. Moreover, DICR is induced by HIV-1 in CD4+ T cells and promotes virus replication in this cell type. Nothing is known hitherto about the DCIR-dependent signaling, which is induced following HIV-1 ligation. First, specific pharmacologic inhibitors were tested on HIV-1 binding/entry and, second, specific antisense oligonucleotides targeted, more specifically kinases and phosphatases, were used. Our results show that SHP-1, SHP-2, Syk, and Src kinases (ie, Src, Fyn, and Hck) as well as PKC-α and MAP kinases (ie, Erk1/2 and p38) are all involved in the DCIR-mediated signal transduction pathway triggered by HIV-1. By mutagenesis and through the use of intracellular phosphorylated peptides, we show as well a pivotal role for the tyrosine and threonine residues of the DCIR immunoreceptor tyrosine-based inhibitory motif (ITIM). Our data suggest for the first time an involvement of ITIM domain in HIV-1–mediated signaling events and a relationship between phosphorylation events and DCIR function with respect to HIV-1 biology.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-4971eISSN: 1528-0020DOI: 10.1182/blood-2011-01-331363Titel-ID: cdi_crossref_primary_10_1182_blood_2011_01_331363
- Format
- –
- Schlagworte
- Amino Acid Motifs, CD4-Positive T-Lymphocytes - metabolism, CD4-Positive T-Lymphocytes - physiology, Cells, Cultured, Disease Progression, HIV Infections - genetics, HIV Infections - metabolism, HIV Infections - pathology, HIV-1 - growth & development, HIV-1 - physiology, Humans, Lectins, C-Type - chemistry, Lectins, C-Type - genetics, Lectins, C-Type - metabolism, Lectins, C-Type - physiology, Membrane Glycoproteins - chemistry, Membrane Glycoproteins - genetics, Membrane Glycoproteins - metabolism, Membrane Glycoproteins - physiology, Phosphorylation - genetics, Protein Binding - drug effects, Protein Binding - physiology, Protein Interaction Domains and Motifs - genetics, Protein Interaction Domains and Motifs - physiology, Protein Kinase Inhibitors - pharmacology, Protein Kinases - metabolism, Receptors, Immunologic - chemistry, Receptors, Immunologic - genetics, Receptors, Immunologic - metabolism, Receptors, Immunologic - physiology, Signal Transduction - genetics, Signal Transduction - physiology, Tyrosine - metabolism, Tyrosine - physiology, Up-Regulation