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Cell Syst. 2017 Apr 26;4(4):430-444.e5. doi: 10.1016/j.cels.2017.02.011. Epub 2017 Mar 18.

Systematic Analysis of Human Protein Phosphatase Interactions and Dynamics.

Author information

1
Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland.
2
Institute of Molecular Systems Biology, ETH Zurich, Zurich 8093, Switzerland.
3
Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki 00014, Finland.
4
Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland. Electronic address: markku.varjosalo@helsinki.fi.

Abstract

Coordinated activities of protein kinases and phosphatases ensure phosphorylation homeostasis, which, when perturbed, can instigate diseases, including cancer. Yet, in contrast to kinases, much less is known about protein phosphatase functions and their interactions and complexes. Here, we used quantitative affinity proteomics to assay protein-protein interactions for 54 phosphatases distributed across the three major protein phosphatase families, with additional analysis of their 12 co-factors. We identified 838 high-confidence interactions, of which 631, to our knowledge, have not been reported before. We show that inhibiting the activity of phosphatases PP1 and PP2A by okadaic acid disrupts their specific interactions, supporting the potential of therapeutics that target these proteins. Additional analyses revealed candidate physical and functional interaction links to phosphatase-based regulation of several signaling pathways and to human cancer. Our study provides an initial glimpse of the protein interaction landscape of phosphatases and their functions in cellular regulation.

KEYWORDS:

cancer; interactome; protein phosphatase; protein-protein interactions; quantitative proteomics

PMID:
28330616
DOI:
10.1016/j.cels.2017.02.011
[Indexed for MEDLINE]
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