Insulin‐stimulated phosphorylation of initiation factor 4E is mediated by the MAP kinase pathway

Abstract

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 4EBPI, does not lead directly to the release of 4E‐BP1.