MassIVE MSV000080844

Imported Reanalysis Dataset Public PXD004816

Protein abundance of AKT and ERK pathway components governs cell-type-specific regulation of proliferation

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Description

Signaling through the AKT and ERK pathways controls cell proliferation. However, the integrated regulation of this multistep process, involving signal processing, cell growth and cell-cycle progression, is poorly understood. Here we study different murine hematopoietic cell types, in which AKT and ERK signaling is triggered by erythropoietin (Epo). Although these cell types share the molecular network topology for pro-proliferative Epo signaling, they exhibit distinct proliferative responses. Iterating quantitative experiments and mathematical modeling, we identify two molecular sources for cell-type-specific proliferation. First, cell-type-specific protein abundance patterns cause differential signal flow along the AKT and ERK pathways. Second, downstream regulators of both pathways have differential effects on proliferation, suggesting that protein synthesis is rate-limiting for faster-cycling cells while slower cell-cycles are controlled at the G1-S progression. The integrated mathematical model of Epo-driven proliferation explains cell-type-specific effects of targeted AKT and ERK inhibitors and faithfully predicts based on the protein abundance anti-proliferative effects of inhibitors in primary human erythroid progenitor cells. Our findings suggest that the effectiveness of targeted cancer therapy might become predictable from protein abundance patterns. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Human ; CFU-E ; label-free quantification ; proteome ruler

Contact

Principal Investigators:
(in alphabetical order) 		Marcel Schilling, German Cancer Research Center (DKFZ), N/A
Submitting User: ccms

Publications

Adlung L, Kar S, Wagner MC, She B, Chakraborty S, Bao J, Lattermann S, Boerries M, Busch H, Wuchter P, Ho AD, Timmer J, Schilling M, Höfer T, Klingmüller U.
Protein abundance of AKT and ERK pathway components governs cell type-specific regulation of proliferation.
Mol. Syst. Biol. 2017 Jan 24;13(1):904. Epub 2017 Jan 24.

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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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