期刊
GENES TO CELLS
卷 24, 期 1, 页码 82-93出版社
WILEY
DOI: 10.1111/gtc.12655
关键词
cellular functions; insulin signaling; network integration; phosphoproteomic data; phosphorylation; systems biology; Trans-omics
资金
- Japan Science and Technology Corporation [JPMJPR1538]
- Core Research for Evolutional Science and Technology [JPMJCR12W3]
- Japan Society for the Promotion of Science [16K12508, 16H06577, 17H06299, 17H06300, 17H06301, 17H06306, 18H03979, JP15H05582, JP18H05431]
- Research Organization of Information and Systems (ROIS)
- National Institute of Genetics (NIG)
- [18H04801]
- Grants-in-Aid for Scientific Research [16K12508, 17H06306, 18H03979, 17H06300, 16H06577, 17H06301] Funding Source: KAKEN
Cellular signaling regulates various cellular functions via protein phosphorylation. Phosphoproteomic data potentially include information for a global regulatory network from signaling to cellular functions, but a procedure to reconstruct this network using such data has yet to be established. In this paper, we provide a procedure to reconstruct a global regulatory network from signaling to cellular functions from phosphoproteomic data by integrating prior knowledge of cellular functions and inference of the kinase-substrate relationships (KSRs). We used phosphoproteomic data from insulin-stimulated Fao hepatoma cells and identified protein phosphorylation regulated by insulin specifically over-represented in cellular functions in the KEGG database. We inferred kinases for protein phosphorylation by KSRs, and connected the kinases in the insulin signaling layer to the phosphorylated proteins in the cellular functions, revealing that the insulin signal is selectively transmitted via the Pi3k-Akt and Erk signaling pathways to cellular adhesions and RNA maturation, respectively. Thus, we provide a method to reconstruct global regulatory network from signaling to cellular functions based on phosphoproteomic data.
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