title: Glucose and amino acids modulate translation factor activation by growth factors in PC12 cells.
abstract: In PC12 phaeochromocytoma cells, protein synthesis is activated by epidermal and nerve growth factors (EGF and NGF). EGF and NGF also regulate a number of components of the translational machinery in these cells. Here we show that the ability of EGF and NGF to induce the phosphorylation of the 70 kDa ribosomal protein, S6 kinase, and the eukaryotic initiation factor (eIF), 4E-binding protein 1, is dependent upon the presence of amino acids (but not glucose) in the medium. This resembles the regulation of these proteins by insulin, which also requires amino acids. Glucose, but not amino acids, is required for the activation of eIF2B by EGF and NGF. In contrast, EGF and NGF can still activate protein synthesis in the absence of nutrients, suggesting that other regulatory events are important in this. In nutrient-deprived cells, an increase in the phosphorylation of eIF4E, and the assembly of the eIF4F complex by EGF and NGF, coincided with the activation of protein synthesis. In serum-starved cells, activation of protein synthesis, phosphorylation of eIF4E, and formation of the eIF4F complex, were blocked by inhibition of MEK, a component of the extracellular regulated kinase (ERK) signalling pathway. Thus the ERK pathway plays a key role in the regulation of protein synthesis in PC12 cells.
authors.affiliation: Department of Anatomy and Physiology, MSI/Wellcome Trust Building, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK. m.scheperkleijn@dundee.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Kleijn
authors.forename: C G
authors.initials: CG
authors.lastname: Proud
mesh_terms: D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E; D039562:Eukaryotic Initiation Factor-4F; D005947:Glucose / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D016716:PC12 Cells; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases
chemical_list: D000596:Amino Acids; D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; C499526:Eif4ebp1 protein, rat; D020717:Eukaryotic Initiation Factor-2B; D039561:Eukaryotic Initiation Factor-4E; D039562:Eukaryotic Initiation Factor-4F; D006133:Growth Substances; D047908:Intracellular Signaling Peptides and Proteins; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; D011494:Protein Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C546845:mTOR protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D005947:Glucose