Fibroblast growth factor receptors (FGFRs) play a crucial role in tissue homeostasis and organ development by regulating cellular processes, including proliferation, differentiation, and survival. Dys Show more
Fibroblast growth factor receptors (FGFRs) play a crucial role in tissue homeostasis and organ development by regulating cellular processes, including proliferation, differentiation, and survival. Dysregulation of FGFRs contributes to developmental disorders and carcinogenesis. As membrane-bound receptors, they represent promising targets for therapeutic intervention and drug development. This study employed a systematic in silico analysis of publicly available phosphoproteomics datasets to provide a comprehensive overview of the phosphorylation regulatory network of the FGFR family. We identified predominant phosphosites in FGFR1-4 that exhibited differential abundance across diverse experimental conditions, specifically, Y653 in FGFR1; S453, Y586, Y656, and Y657 in FGFR2; S444 and S445 in FGFR3; and S573 in FGFR4. Our analysis identified 32 and 89 significantly co-modulated phosphosites on other proteins with FGFR3 and FGFR4, respectively. Beyond the upstream kinases from the FGFR family, we also identified MAPK1 as a potential upstream kinase of FGFR4. Furthermore, disease enrichment analysis revealed that proteins co-modulated with FGFR3 were primarily involved in skeletal developmental disorders, such as brachydactyly, short toe, and syndactyly of fingers, whereas those associated with FGFR4 were linked to various cancers. Our findings highlight key disease-associated phosphosites within the FGFRs and offer a foundation for advancing phosphosite-focused therapeutic research. Show less