Interaction of 14-3-3 With Signaling Proteins Is Mediated by the Recognition of Phosphoserine

Cell. 1996 Mar 22;84(6):889-97. doi: 10.1016/s0092-8674(00)81067-3.

Abstract

The highly conserved and ubiquitously expressed 14-3-3 family of proteins bind to a variety of proteins involved in signal transduction and cell cycle regulation. The nature and specificity of 14-3-3 binding is, however, not known. Here we show that 14-3-3 is a specific phosphoserine-binding protein. Using a panel of phosphorylated peptides based on Raf-1, we have defined the 14-3-3 binding motif and show that most of the known 14-3-3 binding proteins contain the motif. Peptides containing the motif could disrupt 14-3-3 complexes and inhibit maturation of Xenopus laevis oocytes. These results suggest that the interactions of 14-3-3 with signaling proteins are critical for the activation of signaling proteins. Our findings also suggest novel roles for serine/threonine phosphorylation in the assembly of protein-protein complexes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 14-3-3 Proteins
  • 3T3 Cells / metabolism
  • Amino Acid Sequence
  • Animals
  • Enzyme Inhibitors / metabolism*
  • Female
  • Hybridomas
  • Isomerism
  • Mice
  • Molecular Sequence Data
  • Oocytes / metabolism
  • Phosphopeptides / metabolism
  • Phosphorylation
  • Phosphoserine / metabolism*
  • Protein Binding / physiology
  • Protein-Serine-Threonine Kinases / metabolism
  • Proteins / metabolism*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-raf
  • Sensitivity and Specificity
  • Signal Transduction / physiology*
  • T-Lymphocytes / metabolism
  • Tyrosine 3-Monooxygenase*
  • Xenopus

Substances

  • 14-3-3 Proteins
  • Enzyme Inhibitors
  • Phosphopeptides
  • Proteins
  • Proto-Oncogene Proteins
  • Phosphoserine
  • Tyrosine 3-Monooxygenase
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf