The association of initiation factor 4F with Poly(A)-binding protein is enhanced in serum-stimulated Xenopus kidney cells

Serum stimulation of cultured Xenopus kidney cells results in enhanced phos phorylation of the translational initiation factor (eIF) 4E and promotes a 2.8-fold increase in the binding of the adapter protein eIF4G to eIF4E, to form the functional initiation factor complex eIF4F. Here we demonstrate th e serum-stimulated coisolation of the poly(A)-binding protein (PABP) with t he eIF4F complex. This apparent interaction of PABP with eIF4F suggests tha t a mechanism shown to be important in the control of translation in the ye ast Saccharomyces cerevisiae also operates in vertebrate cells. We also pre sent evidence that the signaling pathways modulating eIF4E phosphorylation and function in Xenopus kidney cells differ from those in several mammalian cell types studied previously. Experiments with the immunosuppressant rapa mycin suggest that the mTOR signaling pathway is involved in serum-promoted eIF4E phosphorylation and association with eIF4G. Moreover, we could find little evidence for regulation of eIF4E function via interaction with the s pecific binding proteins 4E-BP1 or 4E-BP2 in these cells. Although rapamyci n abrogated serum-enhanced rates of protein synthesis and the interaction o f eIF4G with eIF4E, it did not prevent the increase in association of eIF4G with PABP. This suggests that serum stimulates the interaction between eIF 4G and PABP by a distinct mechanism that is independent of both the mTOR pa thway and the enhanced association of eIF4G with eIF4E.