Human procaspase-2 phosphorylation at both S139 and S164 is required for 14-3-3 binding

Biochem Biophys Res Commun. 2017 Nov 18;493(2):940-945. doi: 10.1016/j.bbrc.2017.09.116. Epub 2017 Sep 21.


Procaspase-2 phosphorylation at several residues prevents its activation and blocks apoptosis. This process involves procaspase-2 phosphorylation at S164 and its binding to the scaffolding protein 14-3-3. However, bioinformatics analysis has suggested that a second phosphoserine-containing motif may also be required for 14-3-3 binding. In this study, we show that human procaspase-2 interaction with 14-3-3 is governed by phosphorylation at both S139 and S164. Using biochemical and biophysical approaches, we show that doubly phosphorylated procaspase-2 and 14-3-3 form an equimolar complex with a dissociation constant in the nanomolar range. Furthermore, our data indicate that other regions of procaspase-2, in addition to phosphorylation motifs, may be involved in the interaction with 14-3-3.

Keywords: 14-3-3; Caspase-2; Phosphorylation; Procaspase-2; Protein-protein interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Amino Acid Sequence
  • Binding Sites
  • Caspase 2 / chemistry
  • Caspase 2 / metabolism*
  • Humans
  • Phosphorylation
  • Protein Binding
  • Protein Domains
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism


  • 14-3-3 Proteins
  • Recombinant Proteins
  • Caspase 2