PXD041797-1

PXD041797 is an original dataset announced via ProteomeXchange.

Title	The C-terminal phenylalanine–serine KDBS motif prevents constitutive activation of the FGFR2 proto-oncogene
Description	Dysregulated FGF/FGFR signaling leads to a variety of pathologies. These include cancer as well as congenital syndromes that affect skeleton development, impair the response to injury, and/or result in metabolic disorders. In human cancers, the FGFR genes can be affected by hotspot missense mutations or structural alterations, such as amplifications and fusions/rearrangements. Missense mutations affecting the FGFR extracellular domains (e.g., FGFR3S249C) typically facilitate receptor dimerization and ligand-independent activation whereas kinase domain missense mutations frequently facilitate transition to (e.g., FGFR2N549K) or stabilization of (e.g., FGFR3K650E) an active kinase state. FGFR amplifications result in receptor overexpression. Notably, focal FGFR2 amplifications can also produce C-terminally truncated isoforms owing to genomic breakpoints that perturb intron or the FGFR2 C-terminus-encoding exon 18. FGFR2 and FGFR3 fusion/rearrangement breakpoints typically occur in the I17/E18 hotspot, thus also producing C-terminally truncated receptors. E18-truncated FGFR2 variants (FGFR2E18) indeed act as tumor driver genes. Hence, loss of the C-terminus is vital to render FGFR2 and potentially other FGFRs oncogenic.However, it has remained unclear, which motifs or amino acid residues within the C-terminal tail are most critical to suppress oncogenic FGFR2 signaling. Here we made us of a compendium of Fgfr2E18 and Fgfr2 C-terminal variants to functionally dissect FGFR2E18 signaling and the tumor suppressive nature of the FGFR2 C-terminus.
HostingRepository	PRIDE
AnnounceDate	2025-02-17
AnnouncementXML	Submission_2025-02-17_13:20:05.174.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Onno Bleijerveld
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-25 05:31:19	ID requested
⏵ 1	2025-02-17 13:20:05	announced

Dataset with its publication pending

submitter keyword: Fgfr2 signaling, immunoprecipitation, shotgun, LC-MS/MS

Onno Bleijerveld
contact affiliation	NKI Proteomics Facility, Netherlands Cancer Institute, Amsterdam, The Netherlands
contact email	o.bleijerveld@nki.nl
lab head
Onno Bleijerveld
contact affiliation	The Netherlands Cancer Institute
contact email	o.bleijerveld@nki.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041797
     1. Label: PRIDE project
     2. Name: The C-terminal phenylalanine–serine KDBS motif prevents constitutive activation of the FGFR2 proto-oncogene