title: The association of initiation factor 4F with poly(A)-binding protein is enhanced in serum-stimulated Xenopus kidney cells.
abstract: Serum stimulation of cultured Xenopus kidney cells results in enhanced phosphorylation 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 the serum-stimulated co-isolation of the poly(A)-binding protein (PABP) with the eIF4F complex. This apparent interaction of PABP with eIF4F suggests that a mechanism shown to be important in the control of translation in the yeast Saccharomyces cerevisiae also operates in vertebrate cells. We also present 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 rapamycin 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 specific binding proteins 4E-BP1 or 4E-BP2 in these cells. Although rapamycin abrogated serum-enhanced rates of protein synthesis and the interaction of eIF4G with eIF4E, it did not prevent the increase in association of eIF4G with PABP. This suggests that serum stimulates the interaction between eIF4G and PABP by a distinct mechanism that is independent of both the mTOR pathway and the enhanced association of eIF4G with eIF4E.
authors.affiliation: Biochemistry Laboratory, School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, United Kingdom.
authors.forename: C S
authors.initials: CS
authors.lastname: Fraser
authors.forename: V M
authors.initials: VM
authors.lastname: Pain
authors.forename: S J
authors.initials: SJ
authors.lastname: Morley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001769:Blood; D039562:Eukaryotic Initiation Factor-4F; D006868:Hydrolysis; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010766:Phosphorylation; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D039562:Eukaryotic Initiation Factor-4F; D010448:Peptide Initiation Factors; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; D020123:Sirolimus