Proteomics

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Elucidating Fibroblast Growth Factor-induced kinome dynamics using targeted mass spectrometry and dynamic modeling


ABSTRACT: Fibroblast growth factors (FGFs) are paracrine or endocrine signaling proteins that when activated by their ligands, can elicit a wide range of healthy and disease-related processes such as cell proliferation and the epithelial-to-mesenchymal transition (EMT). The detailed molecular pathway dynamics that coordinate these responses have remained unclear. To elucidate and monitor these dynamics we stimulated MCF-7 breast cancer cells with either FGF2, 3, 4, 10, or 19. Following activation of the receptor, we quantified the kinase activity dynamics of 44 kinases using a targeted mass spectrometry assay. Our system-wide kinase activity data, supplemented with (phopsho)proteomics data, reveal ligand-dependent distinct pathway dynamics, elucidate the involvement of not earlier reported kinases such as MARK, and revise some of the pathway effects on biological outcomes. In addition, logic-based dynamic modeling of the kinome dynamics further verifies the biological goodness-of-fit of the predicted models and reveals tight regulation of the RAF kinase family.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Tim Veth  

LAB HEAD: Maarten Altelaar

PROVIDER: PXD038808 | Pride | 2023-07-02

REPOSITORIES: Pride

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Publications

Elucidating Fibroblast Growth Factor-Induced Kinome Dynamics Using Targeted Mass Spectrometry and Dynamic Modeling.

Veth Tim S TS   Francavilla Chiara C   Heck Albert J R AJR   Altelaar Maarten M  

Molecular & cellular proteomics : MCP 20230615 8


Fibroblast growth factors (FGFs) are paracrine or endocrine signaling proteins that, activated by their ligands, elicit a wide range of health and disease-related processes, such as cell proliferation and the epithelial-to-mesenchymal transition. The detailed molecular pathway dynamics that coordinate these responses have remained to be determined. To elucidate these, we stimulated MCF-7 breast cancer cells with either FGF2, FGF3, FGF4, FGF10, or FGF19. Following activation of the receptor, we q  ...[more]

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