TY - JOUR
T1 - Insulin signaling and the general amino acid control response
T2 - Two distinct pathways to amino acid synthesis and uptake
AU - Malmberg, Sharon E.
AU - Adams, Christopher M.
PY - 2008/7/11
Y1 - 2008/7/11
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M801331200
DO - 10.1074/jbc.M801331200
M3 - Article
C2 - 18480057
AN - SCOPUS:50349087339
SN - 0021-9258
VL - 283
SP - 19229
EP - 19234
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 28
ER -