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Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. - eScholarship
Jessica A. Hamerman,Nadia K. Tchao,Clifford A. Lowell,Lewis L. Lanier +3 more
- Vol. 6, Iss: 6, pp 579-586
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TLDR
This article examined the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs) and found that one or more DAP-pairing receptors negatively regulate signaling through TLRs.Abstract:
DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced higher concentrations of inflammatory cytokines in response to a variety of pathogenic stimuli. Additionally, macrophages deficient in spleen tyrosine kinase (Syk), which signals downstream of DAP12, showed a phenotype identical to that of DAP12-deficient macrophages. DAP12-deficient mice were more susceptible to endotoxic shock and had enhanced resistance to infection by the intracellular bacterium Listeria monocytogenes. These data suggest that one or more DAP12-pairing receptors negatively regulate signaling through TLRs.read more
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Syk Facilitates Influenza A Virus Replication by Restraining Innate Immunity at the Late Stage of Viral Infection
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References
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Journal ArticleDOI
Activating and inhibitory functions of DAP12
Isaiah R. Turnbull,Marco Colonna +1 more
TL;DR: This model extends from previous studies of inhibitory signalling mediated by other adaptors, such as the Fc-receptor γ-chain and CD3ζ, and provides a potential mechanism for the conflicting phenotypes observed in studies of DAP12-deficient mice.
Journal ArticleDOI
DAP12-mediated signal transduction in natural killer cells. A dominant role for the Syk protein-tyrosine kinase.
Daniel W. McVicar,Lynn S. Taylor,Pierre Gosselin,Jami Willette-Brown,Anwar I. Mikhael,Robert L. Geahlen,Mary C. Nakamura,Paul A. Linnemeyer,William E. Seaman,Stephen K. Anderson,John R. Ortaldo,Llewellyn H. Mason +11 more
TL;DR: The data demonstrate the dependence of DAP12-coupled receptors on Syk and suggest that the outcome of Ly49D/DAP12 engagement will be regulated by Cbl and culminate in the activation of transcription factors.
Journal ArticleDOI
Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells
Alexander B. H. Bakker,Elizabeth A. Baker,Grant R. Sutherland,Joseph H. Phillips,Lewis L. Lanier +4 more
TL;DR: The molecular cloning of the myeloid DAP 12-associating lectin-1 (MDL-1), a DAP12-association membrane receptor expressed exclusively in monocytes and macrophages, suggests that signaling via MDL- 1/DAP12 complexes may constitute a significant activation pathway in myeloids cells.
Journal ArticleDOI
Src-family and Syk Kinases in Activating and Inhibitory Pathways in Innate Immune Cells: Signaling Cross Talk
TL;DR: The response of innate immune cells to growth factors, immune complexes, extracellular matrix proteins, cytokines, pathogens, cellular damage, and many other stimuli is regulated by a complex net of intracellular signal transduction pathways regulated by Src-family or Syk tyrosine kinases present in innate cells.
Journal ArticleDOI
Role of ITAM-containing adapter proteins and their receptors in the immune system and bone.
TL;DR: Regulation of osteoclastogenesis by ITAM‐dependent receptors suggests that OCLs, similar to related myeloid cells, are tightly controlled by arrays of receptors that allow them to sense and respond to their local microenvironment like other innate immune cells.