Phosphorylation of the eIF4E‐binding protein PHAS‐I after exposure of PC12 cells to EGF and NGF

Abstract

PHAS‐I or the eIF4E‐binding protein 1 regulates the cap‐binding activity of eIF4E by sequestering eIF4E. Binding of eIF4E to PHAS‐I is regulated by phosphorylation of PHAS‐I. PC12 cells were used to study the signal transduction pathway leading to phosphorylation of PHAS‐I. Both EGF and NGF induced phosphorylation of PHAS‐I. Wortmannin, a PI‐3 kinase inhibitor, staurosporine, a PKC inhibitor, and rapamycin, a FRAP inhibitor all blocked the phosphorylation of PHAS‐I. Of the three inhibitors, only wortmannin was able to inhibit MAPK phosphorylation. This excludes a role for MAPK in NGF‐ and EGF‐induced PHAS‐I phosphorylation in PC12 cells. Apparently, PHAS‐I was phosphorylated in a PI‐3 kinase‐, PKC‐, and FRAP‐dependent manner after EGF or NGF stimulation. Only PI‐3 kinase and FRAP are involved in the regulation of the basal level of PHAS‐I phosphorylation.