TY - JOUR
T1 - Implication of eIF2B rather than eIF4E in the regulation of global protein synthesis by amino acids in L6 myoblasts
AU - Kimball, Scot R.
AU - Horetsky, Rick L.
AU - Jefferson, Leonard S.
PY - 1998/11/20
Y1 - 1998/11/20
N2 - The present study was designed to investigate the mechanism through which leucine and histidine regulate translation initiation in L6 myoblasts. The results show that both amino acids stimulate initiation and coordinately regulate the activity of eukaryotic initiation factor eIF2B. The changes in eIF2B activity could be explained in part by modulation of the phosphorylation state of the α-subunit of eIF2. The activity changes might also be a result of modulation of the phosphorylation state of the eIF2B ε- subunit, because deprivation of either amino acid caused a decrease in eIF2Bε kinase activity. Leucine, but not histidine, additionally caused a redistribution of eIF4E from the inactive eIF4E·4E-BP1 complex to the active eIF4E·eIF4G complex. The redistribution was a result of increased phosphorylation of 4E-BP1. The changes in 4E-BP1 phosphorylation and eIF4E redistribution associated with leucine deprivation were not observed in the presence of insulin. However, the leucine- and histidine-induced alterations in global protein synthesis and eIF2B activity were maintained in the presence of the hormone. Overall, the results suggest that both leucine and histidine regulate global protein synthesis through modulation of eIF2B activity. Furthermore, under the conditions employed herein, alterations in eIF4E availability are not rate-controlling for global protein synthesis but might be necessary for regulation of translation of specific mRNAs.
AB - The present study was designed to investigate the mechanism through which leucine and histidine regulate translation initiation in L6 myoblasts. The results show that both amino acids stimulate initiation and coordinately regulate the activity of eukaryotic initiation factor eIF2B. The changes in eIF2B activity could be explained in part by modulation of the phosphorylation state of the α-subunit of eIF2. The activity changes might also be a result of modulation of the phosphorylation state of the eIF2B ε- subunit, because deprivation of either amino acid caused a decrease in eIF2Bε kinase activity. Leucine, but not histidine, additionally caused a redistribution of eIF4E from the inactive eIF4E·4E-BP1 complex to the active eIF4E·eIF4G complex. The redistribution was a result of increased phosphorylation of 4E-BP1. The changes in 4E-BP1 phosphorylation and eIF4E redistribution associated with leucine deprivation were not observed in the presence of insulin. However, the leucine- and histidine-induced alterations in global protein synthesis and eIF2B activity were maintained in the presence of the hormone. Overall, the results suggest that both leucine and histidine regulate global protein synthesis through modulation of eIF2B activity. Furthermore, under the conditions employed herein, alterations in eIF4E availability are not rate-controlling for global protein synthesis but might be necessary for regulation of translation of specific mRNAs.
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U2 - 10.1074/jbc.273.47.30945
DO - 10.1074/jbc.273.47.30945
M3 - Article
C2 - 9812990
AN - SCOPUS:0032553411
SN - 0021-9258
VL - 273
SP - 30945
EP - 30953
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 47
ER -