title: Cellular stress in xenopus kidney cells enhances the phosphorylation of eukaryotic translation initiation factor (eIF)4E and the association of eIF4F with poly(A)-binding protein.
abstract: Eukaryotic initiation factor (eIF) 4E binds to the 5'-cap structure of eukaryotic mRNA and has a central role in the control of cell proliferation. We have shown previously that the stimulation of cultured Xenopus kidney cells with serum resulted in the activation of protein synthesis, enhanced phosphorylation of eIF4E and increased binding of the adapter protein, eIF4G, and poly(A)-binding protein (PABP) to eIF4E to form the functional initiation factor complex, eIF4F/PABP. We now show that cellular stresses such as arsenite, anisomycin and heat shock also result in increased phosphorylation of eIF4E, eIF4F complex formation and the association of PABP with eIF4G, in conditions under which the rate of protein synthesis is severely inhibited. In contrast with reported effects on mammalian cells, the stress-induced increase in eIF4F complex formation occurs in the absence of changes in the association of eIF4E with its binding proteins 4E-BP1 or 4E-BP2. The stress-induced changes in eIF4E phosphorylation were totally abrogated by the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580, and were partly inhibited by the phosphoinositide 3-kinase inhibitor LY294002 and the mammalian target of rapamycin (mTOR) inhibitor rapamycin. However, eIF4E phosphorylation was unaffected by extracellular signal-regulated protein kinase (MAP kinase) inhibitor PD98059. These results indicate that cellular stresses activate multiple signalling pathways that converge at the level of eIF4F complex formation to influence the interactions between eIF4E, eIF4G and PABP.
authors.affiliation: Biochemistry Laboratory, School of Biological Sciences, University of Sussex, Falmer, Brighton, East Sussex BN1 9QG, U.K.
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: D000818:Animals; D000841:Anisomycin / Q000633:toxicity; D018053:Arsenites / Q000633:toxicity; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D039561:Eukaryotic Initiation Factor-4E; D039562:Eukaryotic Initiation Factor-4F; D006358:Hot Temperature; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D010448:Peptide Initiation Factors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D039102:Poly(A)-Binding Proteins; D011494:Protein Kinases; D011725:Pyridines / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014982:Xenopus laevis; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000841:Anisomycin; D018053:Arsenites; D002867:Chromones; D004791:Enzyme Inhibitors; D039561:Eukaryotic Initiation Factor-4E; D039562:Eukaryotic Initiation Factor-4F; D007093:Imidazoles; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D010448:Peptide Initiation Factors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor); D039102:Poly(A)-Binding Proteins; D011494:Protein Kinases; D011725:Pyridines; D016601:RNA-Binding Proteins; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C015001:arsenite; C093642:SB 203580