PXD006157

PXD006157 is an original dataset announced via ProteomeXchange.

Title	The phosphatase PTPRG controls FGFR1 activity and influences sensitivity to FGFR kinase inhibitors
Description	Recently, FGFR1 has been found to be overexpressed in osteosarcoma and thus represents an important target for precision medicine. However, because targeted cancer therapy based on FGFR inhibitors has so far been less efficient than expected, a detailed understanding of the target is important. We have here applied proximity labelling of FGFR1 in an osteosarcoma cell line to identify determinants of FGFR1 activity. Many known FGFR interactors were identified (e.g. FRS2, PLC, RSK2, SHC4, SRC), but the data also suggested novel determinants. A strong hit in our screen was the tyrosine phosphatase PTPRG. We show that PTPRG and FGFR1 interact and colocalize at the plasma membrane where PTPRG directly dephosphorylates activated FGFR1. We further show that osteosarcoma cell lines depleted for PTPRG display increased FGFR activity and are hypersensitive to stimulation by FGF1. In addition, PTPRG depletion elevated cell growth and negatively affected the efficacy of FGFR kinase inhibitors. Thus, PTPRG may have future clinical relevance by being a predictor of outcome after FGFR inhibitor treatment.
HostingRepository	PRIDE
AnnounceDate	2018-01-29
AnnouncementXML	Submission_2018-01-31_00:27:01.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gustavo De Souza
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-22 09:37:25	ID requested
⏵ 1	2018-01-31 00:27:02	announced

Kostas M, Haugsten EM, Zhen Y, S, ø, rensen V, Szybowska P, Fiorito E, Lorenz S, Jones N, de Souza GA, Wiedlocha A, Wesche J, Protein Tyrosine Phosphatase Receptor Type G (PTPRG) Controls Fibroblast Growth Factor Receptor (FGFR) 1 Activity and Influences Sensitivity to FGFR Kinase Inhibitors. Mol Cell Proteomics, 17(5):850-870(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: FGFR1, PTPRG, protein interaction, mass spectrometry

Jorgen Wesche
contact affiliation	Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0379 Oslo, Norway
contact email	jorgen.wesche@rr-research.no
lab head
Gustavo De Souza
contact affiliation	Brain Institute, Federal University of Rio Grande do Norte
contact email	gadsouza@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/01/PXD006157

PRIDE project URI

• PRIDE
  1. PXD006157
     1. Label: PRIDE project
     2. Name: The phosphatase PTPRG controls FGFR1 activity and influences sensitivity to FGFR kinase inhibitors