Nutrient-Induced Responses in Eukaryotic Cells pp 113-130

Part of the Topics in Current Genetics book series (TCG, volume 7)

5 Nutrient signaling through mammalian GCN2

  • Scot R. Kimball
  • Tracy G. Anthony
  • Douglas R. Cavener
  • Leonard S. Jefferson
Chapter

Abstract

mGCN2 is the mammalian ortholog of the protein kinase Gcn2p that is activated in Saccharomyces cerevisiae in response to nutrient starvation. In mammalian cells in culture, mGCN2 is also activated by deprivation of essential amino acids. However, in animals in vivo, mGCN2 is not activated by physiological changes in plasma amino acid concentrations such as occur in response to feeding. Instead, mGCN2 is activated in response to feeding a diet lacking single essential amino acids, suggesting that imbalanced plasma essential amino acid levels are involved in the response. The only known substrate for mGCN2 is the α-subunit of the translation initiation factor, eIF2. Hyperphosphorylation of eIF2α represses the translation of most mRNAs. However, in both yeast and mammals, amino acid deprivation results in only partial phosphorylation of eIF2α, such that the translation of most mRNAs is incompletely repressed. Moreover, the translation of a few mRNAs is enhanced by eIF2α phosphorylation, in particular translation of the mRNAs encoding the transcription factors Gcn4p and ATF4 is stimulated in yeast and mammals, respectively, in response to amino acid deprivation. In each case, the genes induced by the transcription factors provide a mechanism for relieving the stress induced by nutrient starvation.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag Berlin/Heidelberg 2004

Authors and Affiliations

  • Scot R. Kimball
    • 1
  • Tracy G. Anthony
    • 1
  • Douglas R. Cavener
    • 2
  • Leonard S. Jefferson
    • 1
  1. 1.Department of Cellular and Molecular Physiology, Mailcode H166, The Pennsylvania State University College of Medicine, Hershey, PA 17033USA
  2. 2.Department of Biology, The Pennsylvania State University, University Park, PA 16802, USAUSA

Personalised recommendations