Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse Mitotic Regulators

Cell Rep. 2016 Nov 22;17(9):2488-2501. doi: 10.1016/j.celrep.2016.10.078.


Reversible phosphorylation is a fundamental regulatory mechanism, intricately coordinated by kinases and phosphatases, two classes of enzymes widely disrupted in human disease. To better understand the functions of the relatively understudied phosphatases, we have used complementary affinity purification and proximity-based interaction proteomics approaches to generate a physical interactome for 140 human proteins harboring phosphatase catalytic domains. We identified 1,335 high-confidence interactions (1,104 previously unreported), implicating these phosphatases in the regulation of a variety of cellular processes. Systematic phenotypic profiling of phosphatase catalytic and regulatory subunits revealed that phosphatases from every evolutionary family impinge on mitosis. Using clues from the interactome, we have uncovered unsuspected roles for DUSP19 in mitotic exit, CDC14A in regulating microtubule integrity, PTPRF in mitotic retraction fiber integrity, and DUSP23 in centriole duplication. The functional phosphatase interactome further provides a rich resource for ascribing functions for this important class of enzymes.

Keywords: CDC14A; DUSP19; DUSP23; PLK4; PTPRF; interactome; mitosis; phosphatase; phosphorylation; proteomics.

MeSH terms

  • Biological Evolution
  • Centrioles / metabolism
  • Dual-Specificity Phosphatases / metabolism
  • HeLa Cells
  • Humans
  • Mitosis*
  • Phenotype
  • Phosphoric Monoester Hydrolases / metabolism*
  • Protein Binding
  • Protein Interaction Maps*
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Subunits / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism
  • Reproducibility of Results


  • Protein Subunits
  • PLK4 protein, human
  • Protein Serine-Threonine Kinases
  • Phosphoric Monoester Hydrolases
  • DUSP23 protein, human
  • Dual-Specificity Phosphatases
  • PTPRF protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2