The kinase CK1É› controls the antiviral immune response by phosphorylating the signaling adaptor TRAF3.
The signaling adaptor TRAF3 is a highly versatile regulator of both innate immunity and adaptive immunity, but how its phosphorylation is regulated is still unknown. Here we report that deficiency in or inhibition of the conserved serine-threonine kinase CK1É› suppressed the production of type I interferon in response to viral ... infection. CK1É› interacted with and phosphorylated TRAF3 at Ser349, which thereby promoted the Lys63 (K63)-linked ubiquitination of TRAF3 and subsequent recruitment of the kinase TBK1 to TRAF3. Consequently, CK1É›-deficient mice were more susceptible to viral infection. Our findings establish CK1É› as a regulator of antiviral innate immune responses and indicate a novel mechanism of immunoregulation that involves CK1É›-mediated phosphorylation of TRAF3.
Mesh Terms:
Animals, Casein Kinase Iepsilon, Enzyme-Linked Immunosorbent Assay, HEK293 Cells, HeLa Cells, Herpes Simplex, Herpesvirus 1, Human, Humans, Immunity, Innate, Interferon Type I, Interferon-beta, Mass Spectrometry, Mice, Mice, Knockout, Phosphorylation, Protein-Serine-Threonine Kinases, Real-Time Polymerase Chain Reaction, Rhabdoviridae Infections, TNF Receptor-Associated Factor 3, Ubiquitination, Vesiculovirus, West Nile Fever, West Nile virus
Animals, Casein Kinase Iepsilon, Enzyme-Linked Immunosorbent Assay, HEK293 Cells, HeLa Cells, Herpes Simplex, Herpesvirus 1, Human, Humans, Immunity, Innate, Interferon Type I, Interferon-beta, Mass Spectrometry, Mice, Mice, Knockout, Phosphorylation, Protein-Serine-Threonine Kinases, Real-Time Polymerase Chain Reaction, Rhabdoviridae Infections, TNF Receptor-Associated Factor 3, Ubiquitination, Vesiculovirus, West Nile Fever, West Nile virus
Nat. Immunol.
Date: Apr. 01, 2016
PubMed ID: 26928339
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