biostudies-literatureWatson JMedical Research CouncilRCUK | Biotechnology and Biological Sciences Research CouncilRCUK | Medical Research CouncilWellcome TrustBiotechnology and Biological Sciences Research Council6589https://www.ebi.ac.uk/biostudies/studies/S-EPMC9633600biostudies-literatureUnknown13(1)Receptor Tyrosine Kinase (RTK) endocytosis-dependent signalling drives cell proliferation and motility during development and adult homeostasis, but is dysregulated in diseases, including cancer. The recruitment of RTK signalling partners during endocytosis, specifically during recycling to the plasma membrane, is still unknown. Focusing on Fibroblast Growth Factor Receptor 2b (FGFR2b) recycling, we reveal FGFR signalling partners proximal to recycling endosomes by developing a Spatially Resolved Phosphoproteomics (SRP) approach based on APEX2-driven biotinylation followed by phosphorylated peptides enrichment. Combining this with traditional phosphoproteomics, bioinformatics, and targeted assays, we uncover that FGFR2b stimulated by its recycling ligand FGF10 activates mTOR-dependent signNature communicationsSpatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival.PMC9633600107636/Z/15/ABB/R015864/1107636/Z/15/ZMR/T016043/1Fullwood PFerguson HRFrancavilla CHowell GBrady RMFerguson JSchwartz JMSmith MPBexley KHMo HWatson JKnight DfalseSpatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival.Receptor Tyrosine Kinase (RTK) endocytosis-dependent signalling drives cell proliferation and motility during development and adult homeostasis, but is dysregulated in diseases, including cancer. The recruitment of RTK signalling partners during endocytosis, specifically during recycling to the plasma membrane, is still unknown. Focusing on Fibroblast Growth Factor Receptor 2b (FGFR2b) recycling, we reveal FGFR signalling partners proximal to recycling endosomes by developing a Spatially Resolved Phosphoproteomics (SRP) approach based on APEX2-driven biotinylation followed by phosphorylated peptides enrichment. Combining this with traditional phosphoproteomics, bioinformatics, and targeted assays, we uncover that FGFR2b stimulated by its recycling ligand FGF10 activates mTOR-dependent sign2022-01-01T00:00:00Z2022 Nov2025-04-21T23:34:24.297Z2025-02-19T00:32:06.542ZS-EPMC96336003632902810.1038/s41467-022-34298-2