Insulin stimulates protein synthesis in skeletal muscle by enhancing the association of eIF-4E and eIF-4G.
Insulin stimulated protein synthesis in gastrocnemius muscle of perfused rat hindlimb preparations by approximately twofold. The stimulation of protein synthesis was associated with a 12-fold increase in the amount of eukaryotic initiation factor eIF-4G bound to the mRNA cap-binding protein eIF-4E. In part, the increased binding of eIF-4G to eIF-4E was a result of release of eIF-4E bound to the translational regulator, PHAS-I, through a mechanism involving enhanced phosphorylation of PHAS-I. However, the insulin-induced association of eIF-4E and eIF-4G was not due to increased net phosphorylation of eIF-4E because insulin decreased the amount present in the phosphorylated form from 86 to 59% of total eIF-4E. Overall, the results suggest that insulin stimulates protein synthesis in gastrocnemius muscle through a mechanism involving increased binding of eIF-4G to eIF-4E, which is in part due to phosphorylation of PHAS-I, resulting in a release of eIF-4E from the inactive PHAS-I x eIF-4E complex.
Kimball
S R
SR
Department of Cellular and Molecular Physiology, The Pennsylvania State University, College of Medicine, Hershey 17033, USA.
Jurasinski
C V
CV
Lawrence
J C
JC
Jefferson
L S
LS
D000818:Animals; D002352:Carrier Proteins; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D006614:Hindlimb; D007328:Insulin / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D010448:Peptide Initiation Factors; D010750:Phosphoproteins