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Reconstruction of global regulatory network from signaling to cellular functions using phosphoproteomic data
Author(s) -
Kawata Kentaro,
Yugi Katsuyuki,
Hatano Atsushi,
Kokaji Toshiya,
Tomizawa Yoko,
Fujii Masashi,
Uda Shinsuke,
Kubota Hiroyuki,
Matsumoto Masaki,
Nakayama Keiichi I.,
Kuroda Shinya
Publication year - 2019
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12655
Subject(s) - biology , phosphorylation , microbiology and biotechnology , kinase , signal transduction , insulin receptor , kegg , cell signaling , computational biology , biochemistry , insulin , gene expression , transcriptome , gene , insulin resistance , endocrinology
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.