Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function.
The cloning is described of two related human complementary DNAs encoding polypeptides that interact specifically with the translation initiation factor eIF-4E, which binds to the messenger RNA 5'-cap structure. Interaction of these proteins with eIF-4E inhibits translation but treatment of cells with insulin causes one of them to become hyperphosphorylated and dissociate from eIF-4E, thereby relieving the translational inhibition. The action of this new regulator of protein synthesis is therefore modulated by insulin, which acts to stimulate the overall rate of translation and promote cell growth.
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Department of Biochemistry, McGill University, Montréal, Québec, Canada.
Belsham
G J
GJ
Gingras
A C
AC
Donzé
O
O
Lin
T A
TA
Lawrence
J C
JC
Sonenberg
N
N
D000135:Acid Phosphatase / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000273:Adipose Tissue / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004926:Escherichia coli; D039561:Eukaryotic Initiation Factor-4E; D006801:Humans; D007328:Insulin / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000502:physiology*; D012315:RNA Caps / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; C087000:EIF4EBP1 protein, human; C499526:Eif4ebp1 protein, rat; D039561:Eukaryotic Initiation Factor-4E; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; D012315:RNA Caps; D000135:Acid Phosphatase