Insulin signaling and the general amino acid control response. Two distinct pathways to amino acid synthesis and uptake

Sharon E Malmberg; Christopher M Adams

doi:10.1074/jbc.M801331200

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Insulin signaling and the general amino acid control response. Two distinct pathways to amino acid synthesis and uptake

Journal article

Open access

Peer reviewed

Insulin signaling and the general amino acid control response. Two distinct pathways to amino acid synthesis and uptake

Sharon E Malmberg and Christopher M Adams

The Journal of biological chemistry, Vol.283(28), pp.19229-19234

07/11/2008

DOI: 10.1074/jbc.M801331200

PMID: 18480057

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Abstract

ATF4 is a transcription factor that induces a genetic program for amino acid synthesis and amino acid uptake. Previous work demonstrated that ATF4 expression is increased either by insulin or by the general amino acid control (GAAC) response, an evolutionarily ancient pathway that is activated when eukaryotic cells are deprived of amino acids. It is not known whether insulin and the GAAC pathway increase ATF4 expression by the same or different mechanisms. In these studies, we demonstrate that insulin-mediated ATF4 expression occurs as part of a coordinated anabolic program that does not require an essential component of the GAAC pathway, the protein kinase GCN2. Moreover, insulin and the GAAC pathway have an additive effect on expression of ATF4 and downstream mRNAs for amino acid synthesis and uptake. These data suggest that the GAAC pathway may facilitate insulin-mediated anabolism when exogenous amino acids are limiting. We conclude that insulin signaling and the GAAC response comprise two distinct yet complimentary pathways to ATF4 expression, allowing anabolism to be finely tuned to amino acid availability.

Insulin - pharmacology

Hypoglycemic Agents - metabolism

Gene Expression Regulation - physiology

L Cells (Cell Line)

Amino Acids - biosynthesis

Hypoglycemic Agents - pharmacology

Gene Expression Regulation - drug effects

Insulin - metabolism

Animals

Activating Transcription Factor 4 - metabolism

Signal Transduction - drug effects

Signal Transduction - physiology

Mice

Protein-Serine-Threonine Kinases - metabolism

Details

Title: Subtitle: Insulin signaling and the general amino acid control response. Two distinct pathways to amino acid synthesis and uptake
Creators: Sharon E Malmberg - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA
Christopher M Adams
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.283(28), pp.19229-19234
DOI: 10.1074/jbc.M801331200
PMID: 18480057
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Language: English
Date published: 07/11/2008
Academic Unit: Molecular Physiology and Biophysics; Internal Medicine
Record Identifier: 9984025588802771

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