14-3-3 proteins are required for maintenance of Raf-1 phosphorylation and kinase activity Academic Article uri icon

Overview

MeSH Major

  • Protein Structure, Secondary
  • Proteins
  • Proto-Oncogene Proteins c-raf
  • Tyrosine 3-Monooxygenase

abstract

  • By binding to serine-phosphorylated proteins, 14-3-3 proteins function as effectors of serine phosphorylation. The exact mechanism of their action is, however, still largely unknown. Here we demonstrate a requirement for 14-3-3 for Raf-1 kinase activity and phosphorylation. Expression of dominant negative forms of 14-3-3 resulted in the loss of a critical Raf-1 phosphorylation, while overexpression of 14-3-3 resulted in enhanced phosphorylation of this site. 14-3-3 levels, therefore, regulate the stoichiometry of Raf-1 phosphorylation and its potential activity in the cell. Phosphorylation of Raf-1, however, was insufficient by itself for kinase activity. Removal of 14-3-3 from phosphorylated Raf abrogated kinase activity, whereas addition of 14-3-3 restored it. This supports a paradigm in which the effects of phosphorylation on serine as well as tyrosine residues are mediated by inducible protein-protein interactions.

publication date

  • September 1998

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC109108

PubMed ID

  • 9710607

Additional Document Info

start page

  • 5229

end page

  • 38

volume

  • 18

number

  • 9