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Phosphoproteomic profiling of mouse primary HSPCs reveals new regulators of HSPC mobilization

Wang, Leo D. and Ficarro, Scott B. and Hutchinson, John N. and Csépányi-Kömi, Roland and Nguyen, Phi T. and Wisniewski, Eva and Sullivan, Jessica and Hofmann, Oliver and Ligeti, Erzsébet (2016) Phosphoproteomic profiling of mouse primary HSPCs reveals new regulators of HSPC mobilization. BLOOD, 128 (11). pp. 1465-1474. ISSN 0006-4971

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Abstract

Protein phosphorylation is a central mechanism of signal transduction that both positively and negatively regulates protein function. Large-scale studies of the dynamic phosphorylation states of cell signaling systems have been applied extensively in cell lines and whole tissues to reveal critical regulatory networks, and candidate-based evaluations of phosphorylation in rare cell populations have also been informative. However, application of comprehensive profiling technologies to adult stem cell and progenitor populations has been challenging, due in large part to the scarcity of such cells in adult tissues. Here, we combine multi-color flow cytometry with highly efficient three dimensional HPLC/mass spectrometry to enable quantitative phosphoproteomic analysis from 200,000 highly purified primary mouse hematopoietic stem and progenitor cells (HSPCs). Using this platform, we identify ARHGAP25 as a novel regulator of HSPC mobilization and demonstrate that ARHGAP25 phosphorylation at serine 363 is an important modulator of its function. Our approach provides a robust platform for large-scale phosphoproteomic analyses performed with limited numbers of rare progenitor cells. Data from our study comprises a new resource for understanding the molecular signaling networks that underlie hematopoietic stem cell mobilization.

Item Type: Article
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában > R850-854 Experimental medicine / kisérleti orvostudomány
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 19 Feb 2018 08:08
Last Modified: 19 Feb 2018 08:08
URI: http://real.mtak.hu/id/eprint/74666

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