Structure,expression pattern and biological activity of molecular complex TREM-2/DAP12 |
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| Authors: | Agnieszka Paradowska-Gorycka Monika Jurkowska |
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| Affiliation: | Department of Biochemistry and Molecular Biology, Institute of Rheumatology, Warsaw, Poland |
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| Abstract: | DNAX-activating protein of 12 kDa (DAP12) is a member of type I transmembrane adapter proteins containing immunoreceptor tyrosine-based activation motifs (ITAMs). In humans DAP12 gene is located on chromosome 19q13.1. DAP12 forms a molecular complex with triggering receptor expressed on myeloid cells two (TREM-2). TREM-2 ligation leads to the activation of Src family kinases, phosphorylation of tyrosine residues in the ITAM of DAP12, recruitment of the Syk and ZAP70 tyrosine kinases and initiation of an intracellular signaling cascade. Depending on the cell type, DAP12/TREM-2 activation plays an important role in activation and differentiation of osteoclasts, phagocytosis of bacteria, brain and bone homeostasis and inhibition of the toll-like receptor (TLR) signaling in macrophages and dendritic cells. A proper understanding of the function of this complex receptor has been restrained because of the elusive nature of TREM-2 ligands. |
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| Keywords: | BM-DCs, bone marrow-derived DCs CARD9, caspase recruitment domain-containing protein 9 DAG, diacylglycerol DAP12, DNAX-activating protein of 12 kDa DCs, dendritic cells Erk1/2, extracellular signac-regulated kinase 1 and 2 Gads, RGB-2-related adapter downstream of She protein GRB2, growth-factor-receptor-bound protein 2 IFN-γ, interferon-γ IL, interleukin IP3, inositol (1,4,5)-triphosphate ITAM, immunoreceptor tyrosine-based activation motif ITIM, immunoreceptortyrosine-based inhibitory motif Itk, IL-2-induced tyrosine kinase LAB, linker for activation of B-cells LAT, linker for activation of T cells LPS, lipopolisaccharide MAIR-II, myeloid-associated Ig-like receptor II MAPK, mitogen-activated protein kinases MyD88, myeloid differentiation primary response gene (88) NF-κB, nuclear factor-κB NFAT, nuclear factor of activated T-cells NK, natural killer NOS2, NO synthase-2 PDK-1, phosphoinositide-dependent protein kinase-1 PI3K, phosphatidylinositol 3-kinase PIP2, phosphatidylinositol-4,5-bisphosphate PIP3, phosphatidylinositol-3,4,5-trisphosphate PKCθ, protein kinase C θ PLC-γ, phospholipase C-γ RANK, receptor activator for nuclear factor κB SH2, src homology domain-2 SHIP1, SH2 domain-containing inositol phosphatase-1 SLP-76, SH-2 domain-containing leukocyte protein of 76 kDa SOS, son of sevenless homologue Syk, spleen family kinases TCR, T-cell receptor TIRAP, toll-interleukin 1 receptor (TIR) domain containing adaptor protein TLR, toll-like receptor TNF-α, tumor necrosis factor α TREM-2, triggering receptor expressed on myeloid cells 2 ZAP70, δ-chain associated protein kinase of 70 kDa |
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