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 cIF4E is not significantly affected by rapamycin, but is sensitive to wortmannin, which inhibits phosphatidglinositol 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.