DOK3 maintains intestinal homeostasis by suppressing JAK2/STAT3 signaling and S100a8/9 production in neutrophils.

How pathogenesis of inflammatory bowel disease (IBD) depends on the complex interplay of host genetics, microbiome and the immune system is not fully understood. Here, we showed that Downstream of Kinase 3 (DOK3), an adapter protein involved in immune signaling, confers protection of mice from dextran sodium sulfate (DSS)-induced colitis. DOK3-deficiency promotes gut microbial dysbiosis and enhanced colitis susceptibility, which can be reversed by the transfer of normal microbiota from wild-type mice.

TACI Constrains T17 Pathogenicity and Protects against Gut Inflammation.

TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) plays critical roles in B cells by promoting immunoglobulin class switching and plasma cell survival. However, its expression and function in T cells remain controversial. We show here that TACI expression can be strongly induced in murine CD4 T cells by cytokines responsible for T17 but not T1 or T2 differentiation.

Dok3-protein phosphatase 1 interaction attenuates Card9 signaling and neutrophil-dependent antifungal immunity.

Invasive fungal infection is a serious health threat with high morbidity and mortality. Current antifungal drugs only demonstrate partial success in improving prognosis. Furthermore, mechanisms regulating host defense against fungal pathogens remain elusive.

The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance interferon-β response.

RIG-I senses viral RNA in the cytosol and initiates host innate immune response by triggering the production of type 1 interferon. A recent RNAi knockdown screen yielded close to hundred host genes whose products affected viral RNA-induced IFN-β production and highlighted the complexity of the antiviral response. The stress granule protein G3BP1, known to arrest mRNA translation, was identified as a regulator of RIG-I-induced IFN-β production.

Quantitative and Label-Free Detection of Protein Kinase A Activity Based on Surface-Enhanced Raman Spectroscopy with Gold Nanostars.

The activity of extracellular protein kinase A (PKA) is known to be a biomarker for cancer. However, conventional PKA assays based on colorimetric, radioactive, and fluorometric techniques suffer from intensive labeling-related preparations, background interference, photobleaching, and safety concerns. While surface-enhanced Raman spectroscopy (SERS)-based assays have been developed for various enzymes to address these limitations, their use in probing PKA activity is limited due to subtle changes in the Raman spectrum with phosphorylation.

ArfGAP Domain-Containing Protein 2 (ADAP2) Integrates Upstream and Downstream Modules of RIG-I Signaling and Facilitates Type I Interferon Production.

Transcription of type I interferon genes during RNA virus infection requires signal communication between several pattern recognition receptor (PRR)-adaptor complexes located at distinct subcellular membranous compartments and a central cytoplasmic TBK1-interferon regulatory factor 3 (IRF3) kinase-transcription factor module. However, how the cell integrates signal transduction through spatially distinct modules of antiviral signaling pathways is less defined. RIG-I is a major cytosolic PRR involved in the control of several RNA viruses.

Bruton's tyrosine kinase phosphorylates DDX41 and activates its binding of dsDNA and STING to initiate type 1 interferon response.

The innate immune system senses cytosolic dsDNA and bacterial cyclic dinucleotides and initiates signaling via the adaptor STING to induce type 1 interferon (IFN) response. We demonstrate here that BTK-deficient cells have impaired IFN-β production and TBK1/IRF3 activation when stimulated with agonists or infected with pathogens that activate STING signaling. BTK interacts with STING and DDX41 helicase.

DOK3 is required for IFN-β production by enabling TRAF3/TBK1 complex formation and IRF3 activation.

The downstream of kinase (DOK) family of adaptors is generally involved in the negative regulation of signaling pathways. DOK1, 2, and 3 were shown to attenuate TLR4 signaling by inhibiting Ras-ERK activation. In this study, we elucidated a novel role for DOK3 in IFN-β production.