Activation of a novel ULK1-MLK3-ERK5 pathway by the IFNg receptor is required for IFNg-inducible antiviral responses

Although well established that signal transducer and activator of transcription 1 (STAT1) activation is required for an interferon (IFN)-mediated antiviral response, the potential roles of other IFNg-activated cellular pathways in the process are unknown. We provide evidence that Unc-51-like kinase 1 (ULK1) is activated during engagement of the Type II IFN receptor and is required for IFNg-mediated transcription of key interferon stimulated genes involved in anti-viral and innate immune responses. Ulk1/2+/+ and Ulk1/2-/- mouse embryonic fibroblasts (MEFs) were plated as four biological replicates and were either left untreated or were treated for 6 hours with 2.5x103 IU/ml of mouse IFNg, followed by total RNA isolation. Total mRNA profiles of untreated versus IFNg-treated Ulk1/2+/+ and Ulk1/2-/- MEFs were then generated by deep sequencing, using Illumina NextSeq 500.