A phospho-tyrosine-based signaling module using SPOP, CSK, and LYN controls TLR-induced IRF activity.

ABSTRACT: Toll-like receptors (TLRs) recognize pathogen- and host-derived factors and control immune responses via the adaptor protein MyD88 and members of the interferon regulatory transcription factor (IRF) family. IRFs orchestrate key effector functions, including cytokine release, cell differentiation, and, under certain circumstances, inflammation pathology. Here, we show that IRF activity is generically controlled by the Src kinase family member LYN, which phosphorylates all TLR-induced IRFs at a conserved tyrosine residue, resulting in K48-linked polyubiquitination and proteasomal degradation of IRFs. We further show that LYN activity is controlled by the upstream kinase C-terminal Src kinase (CSK), whose activity, in turn, is controlled by the adaptor protein SPOP, which serves as molecular

SUBMITTER: Tawaratsumida K 

PROVIDER: S-EPMC9269885 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature