title: The 14-3-3 proteins in regulation of cellular metabolism.
abstract: 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.
authors: Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.
authors: Rune
authors: R
authors: Kleppe
authors: Aurora
authors: A
authors: Martinez
authors: Stein Ove
authors: SO
authors: Døskeland
authors: Jan
authors: J
authors: Haavik
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D002462:Cell Membrane / Q000378:metabolism; D004734:Energy Metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048948:14-3-3 Proteins; D000596:Amino Acids; D007328:Insulin; D011494:Protein Kinases