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The calcineurin signaling network evolves via conserved kinase‐phosphatase modules that transcend substrate identity (586.3)
Author(s) -
Cyert Martha,
Goldman Aaron,
Roy Jagoree,
Bodenmiller Bernd,
Wanka Stefanie,
Landry Christian,
Aebersold Ruedi
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.586.3
Subject(s) - calcineurin , phosphatase , kinase , dephosphorylation , phosphorylation , biology , microbiology and biotechnology , biochemistry , computational biology , medicine , surgery , transplantation
To define the first functional network for calcineurin, the conserved Ca2+/calmodulin‐regulated phosphatase, we systematically identified its substrates in S. cerevisiae using phosphoproteomics and bioinformatics, followed by co‐purification and dephosphorylation assays. This ‘calcineurinome’ establishes new calcineurin functions and reveals mechanisms that shape calcineurin network evolution. Analyses of closely related yeasts show that many proteins were recently recruited to the calcineurinome by acquiring a calcineurin‐recognition motif. Calcineurin substrates in yeast and mammals are distinct, due to network rewiring, but, surprisingly, are phosphorylated by similar kinases. We postulate that co‐recognition of conserved substrate features, including phosphorylation and docking motifs, preserves calcineurin‐kinase opposition during evolution. One example we document is a composite docking site that confers substrate recognition by both calcineurin and MAPK. We propose that conserved kinase‐phosphatase pairs define the architecture of signaling networks and allow other connections between kinases and phosphatases to develop and establish common regulatory motifs in signaling networks. Grant Funding Source : Supported by NIH 5R01GM048729