Proteomics

Dataset Information

0

The phosphatase PTPRG controls FGFR1 activity and influences sensitivity to FGFR kinase inhibitors


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Gustavo De Souza  

LAB HEAD: Jorgen Wesche

PROVIDER: PXD006157 | Pride | 2018-01-29

REPOSITORIES: Pride

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Publications

Protein Tyrosine Phosphatase Receptor Type G (PTPRG) Controls Fibroblast Growth Factor Receptor (FGFR) 1 Activity and Influences Sensitivity to FGFR Kinase Inhibitors.

Kostas Michal M   Haugsten Ellen Margrethe EM   Zhen Yan Y   Sørensen Vigdis V   Szybowska Patrycja P   Fiorito Elisa E   Lorenz Susanne S   Jones Nina N   de Souza Gustavo Antonio GA   Wiedlocha Antoni A   Wesche Jørgen J  

Molecular & cellular proteomics : MCP 20180125 5


Recently, FGFR1 was found to be overexpressed in osteosarcoma and 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-dependent biotin labeling combined with label-free quantitative mass spectrometry to identify determinants of FGFR1 activity in an osteosarcoma cell line. Many known FGFR interactors  ...[more]

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