Reconstruction of global regulatory network from signaling to cellular functions using phosphoproteomic data

Kentaro Kawata, Katsuyuki Yugi, Atsushi Hatano, Toshiya Kokaji, Yoko Tomizawa, Masashi Fujii, Shinsuke Uda, Hiroyuki Kubota, Masaki Matsumoto, Keiichi Nakayama, Shinya Kuroda

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)82-93
Number of pages12
JournalGenes to Cells
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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Insulin
Phosphorylation
Proteins
Protein Kinases
Hepatocellular Carcinoma
Phosphotransferases
Databases
RNA

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

Cite this

Kawata, K., Yugi, K., Hatano, A., Kokaji, T., Tomizawa, Y., Fujii, M., ... Kuroda, S. (2019). Reconstruction of global regulatory network from signaling to cellular functions using phosphoproteomic data. Genes to Cells, 24(1), 82-93. https://doi.org/10.1111/gtc.12655

Reconstruction of global regulatory network from signaling to cellular functions using phosphoproteomic data. / Kawata, Kentaro; Yugi, Katsuyuki; Hatano, Atsushi; Kokaji, Toshiya; Tomizawa, Yoko; Fujii, Masashi; Uda, Shinsuke; Kubota, Hiroyuki; Matsumoto, Masaki; Nakayama, Keiichi; Kuroda, Shinya.

In: Genes to Cells, Vol. 24, No. 1, 01.01.2019, p. 82-93.

Research output: Contribution to journalArticle

Kawata, Kentaro ; Yugi, Katsuyuki ; Hatano, Atsushi ; Kokaji, Toshiya ; Tomizawa, Yoko ; Fujii, Masashi ; Uda, Shinsuke ; Kubota, Hiroyuki ; Matsumoto, Masaki ; Nakayama, Keiichi ; Kuroda, Shinya. / Reconstruction of global regulatory network from signaling to cellular functions using phosphoproteomic data. In: Genes to Cells. 2019 ; Vol. 24, No. 1. pp. 82-93.
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