Phosphoproteomics analyses show subnetwork systems in T-cell receptor signaling

Atsushi Hatano, Masaki Matsumoto, Keiichi I. Nakayama

研究成果: ジャーナルへの寄稿記事

4 引用 (Scopus)

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A key issue in the study of signal transduction is how multiple signaling pathways are systematically integrated into the cell. We have now performed multiple phosphoproteomics analyses focused on the dynamics of the T-cell receptor (TCR) signaling network and its subsystem mediated by the Ca2+ signaling pathway. Integration of these phosphoproteomics data sets and extraction of components of the TCR signaling network dependent on Ca2+ signaling showed unexpected phosphorylation kinetics for candidate substrates of the Ca2+-dependent phosphatase calcineurin (CN) during TCR stimulation. Detailed characterization of the TCR-induced phosphorylation of a novel CN substrate, Itpkb, showed that phosphorylation of this protein is regulated by both CN and the mitogen-activated protein kinase Erk in a competitive manner. Phosphorylation of additional CN substrates was also found to be regulated by Erk and CN in a similar manner. The combination of multiple phosphoproteomics approaches thus showed two major subsystems mediated by Erk and CN in the TCR signaling network, with these subsystems regulating the phosphorylation of a group of proteins in a competitive manner.

元の言語英語
ページ(範囲)1095-1112
ページ数18
ジャーナルGenes to Cells
21
発行部数10
DOI
出版物ステータス出版済み - 10 1 2016

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

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