Phosphatase SHP-1 promotes TLR- and RIG-I-activated production of type I interferon by inhibiting the kinase IRAK1
- 6 April 2008
- journal article
- Published by Springer Nature in Nature Immunology
- Vol. 9 (5) , 542-550
- https://doi.org/10.1038/ni.1604
Abstract
Unbalanced production of proinflammatory cytokines and type I interferons in immune responses may lead to immunopathology; thus, the mechanisms that ensure the beneficial production of proinflammatory cytokines and type I interferons are of particular importance. Here we demonstrate that the phosphatase SHP-1 negatively regulated Toll-like receptor-mediated production of proinflammatory cytokines by inhibiting activation of the transcription factor NF-kappaB and mitogen-activated protein kinase. Simultaneously, SHP-1 increased the production of type I interferon mediated by Toll-like receptors and the helicase RIG-I by directly binding to and inhibiting activation of the kinase IRAK1. Our data demonstrate that SHP-1 contributes to immune homeostasis by balancing the production of proinflammatory cytokines and type I interferons in the innate immune response.Keywords
This publication has 36 references indexed in Scilit:
- FADD Negatively Regulates Lipopolysaccharide Signaling by Impairing Interleukin-1 Receptor-Associated Kinase 1-MyD88 InteractionMolecular and Cellular Biology, 2007
- Tyrosine kinase Syk associates with toll‐like receptor 4 and regulates signaling in human monocytic cellsImmunology & Cell Biology, 2007
- Antagonism or SynergismJournal of Biological Chemistry, 2006
- IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon inductionNature Immunology, 2005
- Negative regulation of Toll-like receptor-mediated immune responsesNature Reviews Immunology, 2005
- Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-α inductionThe Journal of Experimental Medicine, 2005
- Dual Receptors and Distinct Pathways Mediate Interleukin-1 Receptor-associated Kinase Degradation in Response to LipopolysaccharideJournal of Biological Chemistry, 2004
- Role of Adaptor TRIF in the MyD88-Independent Toll-Like Receptor Signaling PathwayScience, 2003
- Bruton's Tyrosine Kinase Is a Toll/Interleukin-1 Receptor Domain-binding Protein That Participates in Nuclear Factor κB Activation by Toll-like Receptor 4Journal of Biological Chemistry, 2003
- Toll-Like Receptor Signaling PathwaysScience, 2003