Functional proteomics defines the molecular switch underlying FGF receptor trafficking and cellular outputs.

摘要: The stimulation of fibroblast growth factor receptors (FGFRs) with distinct FGF ligands generates specific cellular responses. However, the mechanisms underlying this paradigm have remained elusive. Here, we show that FGF-7 leads to FGFR2b degradation and, ultimately, cell proliferation, whereas FGF-10 promotes receptor recycling and migration. By combining mass-spectrometry-based quantitative proteomics fluorescence microscopy biochemical methods, find specifically induces rapid phosphorylation tyrosine (Y) 734 on FGFR2b, which PI3K SH3BP4 recruitment. This complex is crucial for responses, given either FGFR2b_Y734F mutant- or SH3BP4-depleted cells switches endocytic route degradation, resulting in decreased breast cancer migration inhibition epithelial branching mouse lung explants. Altogether, these results identify an intriguing ligand-dependent mechanism control fate outputs may explain pathogenic role deregulated thus offering therapeutic opportunities.