Mapping the FGF2\nInteractome Identifies a Functional\nProteoglycan Coreceptor

Fibroblast growth factor 2 (FGF2) is a multipotent growth\nfactor\nand signaling protein that exhibits broad functions across multiple\ncell types. These functions are often initiated by binding to growth\nfactor receptors and fine-tuned by glycosaminoglycan (GAG)-modified\nproteins called proteoglycans. The various outputs of FGF2 signaling\nand functions arise from a dynamic and cell type-specific set of binding\npartners. However, the interactome of FGF2 has yet to be comprehensively\ndetermined. Moreover, the identity of the proteoglycan proteins carrying\nGAG chains is often overlooked and remains unknown in most cell contexts.\nHere, we perform peroxidase-catalyzed live cell proximity labeling\nusing an engineered APEX2-FGF2 fusion protein to map the interactome\nof FGF2. Across two cell lines with established and distinct FGF2-driven\nfunctions, we greatly expand upon the known FGF2 interactome, identifying\n>600 new putative FGF2 interactors. Notably, our results demonstrate\na key role for the GAG binding capacity of FGF2 in modulating its\ninteractome.