proteomics and biochemistry
Recorded terms: in vitro kinase assay; in vitro kinase assays; radiolabeled ATP incorporation; recombinant kinase assay
Kinase substrate specificity profiling assigns the phosphorylation cluster in the SARS-CoV-2 nucleocapsid SR-rich domain to a cascade initiated by SRPK1 and SRPK2 and extended by GSK-3 and casein kinase 1, whose inhibition suppresses coronavirus replication.
Phosphorylation of STAT1 serine 708 by IKKε blocks formation of the STAT1 homodimer that constitutes GAF while leaving the STAT1 and STAT2 heterodimer of ISGF3 intact, biasing the shared STAT1 pool and the interferon-stimulated transcriptome toward the type I response.
Mice lacking IKKε produce normal interferon-β but fail to induce roughly a third of interferon-stimulated genes, because interferon activates IKKε, which phosphorylates STAT1 at Ser708 and thereby determines whether ISGF3 occupies a subset of response elements.
The IKK-related kinases IKKepsilon and TBK1 are identified as components of the virus-activated kinase activity that phosphorylates the C-terminal serine cluster of IRF-3 and IRF-7, linking pathogen sensing to type I interferon gene induction and to establishment of an antiviral state.