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.
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Research Article|
April 10 2000
Glucose and amino acids modulate translation factor activation by growth factors in PC12 cells
Miranda KLEIJN;
Miranda KLEIJN
1
1To whom correspondence should be addressed (e-mail m.scheperkleijn@;dundee.ac.uk).
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Christopher G. PROUD
Christopher G. PROUD
1Department of Anatomy and Physiology, MSI/Wellcome Trust Building, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
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Publisher: Portland Press Ltd
Received:
October 18 1999
Revision Received:
January 04 2000
Accepted:
February 02 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 347 (2): 399–406.
Article history
Received:
October 18 1999
Revision Received:
January 04 2000
Accepted:
February 02 2000
Citation
Miranda KLEIJN, Christopher G. PROUD; Glucose and amino acids modulate translation factor activation by growth factors in PC12 cells. Biochem J 15 April 2000; 347 (2): 399–406. doi: https://doi.org/10.1042/bj3470399
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