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Phosphoproteomics analyses show subnetwork systems in T‐cell receptor signaling
Author(s) -
Hatano Atsushi,
Matsumoto Masaki,
Nakayama Keiichi I.
Publication year - 2016
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.12406
Subject(s) - phosphoproteomics , phosphorylation , biology , signal transduction , microbiology and biotechnology , t cell receptor , mapk/erk pathway , cell signaling , protein tyrosine phosphatase , protein phosphorylation , protein kinase a , t cell , immunology , immune system
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 Ca 2+ signaling pathway. Integration of these phosphoproteomics data sets and extraction of components of the TCR signaling network dependent on Ca 2+ signaling showed unexpected phosphorylation kinetics for candidate substrates of the Ca 2+ ‐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.