4.7 Article

Systematic Analysis of Human Protein Phosphatase Interactions and Dynamics

期刊

CELL SYSTEMS
卷 4, 期 4, 页码 430-+

出版社

CELL PRESS
DOI: 10.1016/j.cels.2017.02.011

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资金

  1. Academy of Finland [288475, 294173]
  2. Sigrid Juselius Foundation
  3. University of Helsinki Three-year Research Grant
  4. Biocentrum Helsinki
  5. Biocentrum Finland
  6. Instrumentarium Research Foundation
  7. Academy of Finland (AKA) [294173, 288475, 294173, 288475] Funding Source: Academy of Finland (AKA)

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Coordinated activities of protein kinases and phos-phatases 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 phos-phatase 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 phos-phatasebased 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.

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