Insulin-stimulated phosphorylation of initiation factor 4E is mediated by the MAP kinase pathway.
The cap-binding initiation factor 4E (eIF4E) is regulated by phosphorylation and by the inhibitory binding protein 4E-BP1. Here we show that insulin-induced phosphorylation of eIF4E is not significantly affected by rapamycin, but is sensitive to wortmannin, which inhibits phosphatidylinositol 3'-kinase and blocks the activation of MAP kinase. Since PD098059, an inhibitor of MAP kinase activation, also blocks insulin-induced phosphorylation of eIF4E, the MAP kinase pathway seems to mediate this effect. Phosphorylated eIF4E can still bind to 4E-BP1. These data illustrate that (i) distinct signalling pathways mediate the phosphorylation of eIF4E and 4E-BP1 and (ii) phosphorylation of eIF4E, unlike that of 4E-BP1, does not lead directly to the release of 4E-BP1.
Flynn
A
A
Department of Biosciences, University of Kent at Canterbury, UK.
Proud
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G
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D039561:Eukaryotic Initiation Factor-4E; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D010448:Peptide Initiation Factors / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011090:Polyenes / Q000494:pharmacology; D015398:Signal Transduction; D020123:Sirolimus; D000077191:Wortmannin
D000730:Androstadienes; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D039561:Eukaryotic Initiation Factor-4E; D007328:Insulin; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; D011090:Polyenes; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020123:Sirolimus; D000077191:Wortmannin