{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Batth TS"],"funding":["European Molecular Biology Organization","Horizon 2020 Framework Programme","Kræftens Bekæmpelse","Novo Nordisk Foundation Center for Protein Research","Lundbeckfonden","Novo Nordisk Fonden","Wellcome Trust","Lundbeck Foundation"],"pagination":["2784-2796"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618100"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["22(10)"],"pubmed_abstract":["Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)-initiated signaling networks upon activation by Pdgf-ββ, Fgf-2, or Igf-1 and identified more than 40,000 phosphorylation sites, including many phosphotyrosine sites without additional enrichment. The analysis revealed RTK-specific regulation of hundreds of pTyr sites on key signaling molecules. We found the tyrosine phosphatase Shp-2 to be the master regulator of Pdgfr pTyr signaling. Application of a recently introduced allosteric Shp-2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. In addition, we present a list of hundreds of Shp-2-dependent targets and putative substrates, including Rasa1 and Cortactin with increased pTyr and Gab1 and Erk1/2 with decreased pTyr. Our study demonstrates that large-scale quantitative phosphoproteomics can precisely dissect tightly regulated kinase-phosphatase signaling networks."],"journal":["Cell reports"],"pubmed_title":["Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling."],"pmcid":["PMC7618100"],"funding_grant_id":["R90-A5844","NNF14CC0001","MSmed 686547","8107636/Z/15/Z","107636","R191-2015-703","PI Jesper Velgaard Olsen"],"pubmed_authors":["Papetti M","Olsen JV","Francavilla C","Batth TS","Tollenaere MAX","Pfeiffer A"],"additional_accession":[]},"is_claimable":false,"name":"Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling.","description":"Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)-initiated signaling networks upon activation by Pdgf-ββ, Fgf-2, or Igf-1 and identified more than 40,000 phosphorylation sites, including many phosphotyrosine sites without additional enrichment. The analysis revealed RTK-specific regulation of hundreds of pTyr sites on key signaling molecules. We found the tyrosine phosphatase Shp-2 to be the master regulator of Pdgfr pTyr signaling. Application of a recently introduced allosteric Shp-2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. In addition, we present a list of hundreds of Shp-2-dependent targets and putative substrates, including Rasa1 and Cortactin with increased pTyr and Gab1 and Erk1/2 with decreased pTyr. Our study demonstrates that large-scale quantitative phosphoproteomics can precisely dissect tightly regulated kinase-phosphatase signaling networks.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Mar","modification":"2026-04-20T03:20:24.938Z","creation":"2026-04-20T03:10:14.743Z"},"accession":"S-EPMC7618100","cross_references":{"pubmed":["29514104"],"doi":["10.1016/j.celrep.2018.02.038"]}}