From promiscuity to precision: protein phosphatases get a makeover

Mol Cell. 2009 Mar 13;33(5):537-45. doi: 10.1016/j.molcel.2009.02.015.


The control of biological events requires strict regulation using complex protein phosphorylation and dephosphorylation strategies. The bulk of serine-threonine dephosphorylations are catalyzed by a handful of phosphatase catalytic subunits, giving rise to the misconception that these phosphatases are promiscuous and unregulated enzymes in vivo. The reality is much more nuanced: PP1 and PP2A, the most abundant serine-threonine phosphatases, are, in fact, families of hundreds of protein serine/threonine phosphatases, assembled from a few catalytic subunits in combination with a highly diverse array of regulators. As recent publications illustrate, these regulatory subunits confer specificity, selectivity, localization, and regulation on these important enzymes.

Publication types

  • Review

MeSH terms

  • Animals
  • Catalytic Domain
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Isoenzymes
  • Models, Molecular
  • Phosphoprotein Phosphatases / chemistry
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Protein Conformation
  • Protein Phosphatase 1 / metabolism
  • Protein Phosphatase 2 / metabolism
  • Protein Processing, Post-Translational*
  • Signal Transduction*
  • Substrate Specificity
  • Transforming Growth Factor beta / metabolism
  • tau Proteins / metabolism


  • Intracellular Signaling Peptides and Proteins
  • Isoenzymes
  • Transforming Growth Factor beta
  • tau Proteins
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1
  • Protein Phosphatase 2
  • protein phosphatase 4