The 14-3-3 proteins in regulation of cellular metabolism

Semin Cell Dev Biol. 2011 Sep;22(7):713-9. doi: 10.1016/j.semcdb.2011.08.008. Epub 2011 Aug 22.


Thirty years ago, it was discovered that 14-3-3 proteins could activate enzymes involved in amino acid metabolism. In the following decades, 14-3-3s have been shown to be involved in many different signaling pathways that modulate cellular and whole body energy and nutrient homeostasis. Large scale screening for cellular binding partners of 14-3-3 has identified numerous proteins that participate in regulation of metabolic pathways, although only a minority of these targets have yet been subject to detailed studies. Because of the wide distribution of potential 14-3-3 targets and the resurging interest in metabolic pathway control in diseases like cancer, diabetes, obesity and cardiovascular disease, we review the role of 14-3-3 proteins in the regulation of core and specialized cellular metabolic functions. We cite illustrative examples of 14-3-3 action through their direct modulation of individual enzymes and through regulation of master switches in cellular pathways, such as insulin signaling, mTOR- and AMP dependent kinase signaling pathways, as well as regulation of autophagy. We further illustrate the quantitative impact of 14-3-3 association on signal response at the target protein level and we discuss implications of recent findings showing 14-3-3 protein membrane binding of target proteins.

Publication types

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

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Amino Acids / metabolism
  • Animals
  • Autophagy
  • Cell Membrane / metabolism
  • Energy Metabolism*
  • Humans
  • Insulin / metabolism
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Signal Transduction*


  • 14-3-3 Proteins
  • Amino Acids
  • Insulin
  • Protein Kinases