The extended PP1 toolkit: designed to create specificity

Trends Biochem Sci. 2010 Aug;35(8):450-8. doi: 10.1016/j.tibs.2010.03.002. Epub 2010 May 1.

Abstract

Protein Ser/Thr phosphatase-1 (PP1) catalyzes the majority of eukaryotic protein dephosphorylation reactions in a highly regulated and selective manner. Recent studies have identified an unusually diversified PP1 interactome with the properties of a regulatory toolkit. PP1-interacting proteins (PIPs) function as targeting subunits, substrates and/or inhibitors. As targeting subunits, PIPs contribute to substrate selection by bringing PP1 into the vicinity of specific substrates and by modulating substrate specificity via additional substrate docking sites or blocking substrate-binding channels. Many of the nearly 200 established mammalian PIPs are predicted to be intrinsically disordered, a property that facilitates their binding to a large surface area of PP1 via multiple docking motifs. These novel insights offer perspectives for the therapeutic targeting of PP1 by interfering with the binding of PIPs or substrates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Catalytic Domain*
  • Models, Molecular
  • Protein Binding
  • Protein Phosphatase 1 / antagonists & inhibitors
  • Protein Phosphatase 1 / chemistry*
  • Protein Phosphatase 1 / genetics
  • Protein Phosphatase 1 / metabolism*
  • Substrate Specificity

Substances

  • Protein Phosphatase 1