Spatiotemporal profiling of modification-specific proteome secretion uncovers an itaconation-activated tyrosine kinase.

ABSTRACT: Macrophages secrete diverse signaling proteins critical for intercellular communication and immune responses, processes tightly regulated by post-translational modifications (PTMs). Itaconate, an immunoregulatory metabolite produced in macrophages, induces widespread intracellular protein modification (itaconation), affecting pathways like the KEAP1-NRF2 axis and glycolysis. However, the impact of itaconation on the extracellular proteome and signaling remains poorly characterized. Herein, we introduce PTM-based secretome profiling (PBSP), a novel approach to identify secreted proteins bearing specific PTMs. The method employs a bioorthogonal probe to label modified proteins in live cells, followed by enrichment of labeled proteins from the culture medium upon secretion. We established a s

SUBMITTER: Lu W 

PROVIDER: S-EPMC12686461 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature