Incubation of Chinese hamster ovary cells without amino acids for up to 60 min caused a rapid marked decrease in p70 S6 kinase activity and increased binding of initiation factor eIF4E to its inhibitory regulator protein 4E-BP1. This was associated with dephosphorylation of 4E-BP1 and eIF4E and dissociation of eIF4E from eIF4G. All these effects were rapidly reversed by resupplying a mixture of amino acids and this was blocked by rapamycin and by inhibitors of phosphatidylinositol 3-kinase, implying a role for phosphatidylinositol 3-kinase in the signalling pathway linking amino acids with the control of p70 S6 kinase activity and the phosphorylation of these translation factors. Amino acid withdrawal also led to changes in the phosphorylation of other translation factors; phosphorylation of eIF4E decreased whereas elongation factor eEF2 became more heavily phosphorylated, each of these changes being associated with decreased activity of the factor in question. Earlier studies have suggested that protein kinase B (PKB) may act upstream of p70 S6 kinase. However, amino acids did not affect the activity of PKB, indicating that amino acids activate p70 S6 kinase through a pathway independent of this enzyme. Studies with individual amino acids suggested that the effects on p70 S6 kinase activity and translation-factor phosphorylation were independent of cell swelling. The data show that amino acid supply regulates multiple translation factors in mammalian cells.
Skip Nav Destination
Article navigation
August 1998
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Research Article|
August 15 1998
Amino acid availability regulates p70 S6 kinase and multiple translation factors
Xuemin WANG;
Xuemin WANG
*Department of Anatomy and Physiology, University of Dundee, Dundee DD1 4HN, U.K.
Search for other works by this author on:
Linda E. CAMPBELL;
Linda E. CAMPBELL
*Department of Anatomy and Physiology, University of Dundee, Dundee DD1 4HN, U.K.
Search for other works by this author on:
Christa M. MILLER;
Christa M. MILLER
†Department of Biosciences, University of Kent at Canterbury, Canterbury CT2 7NJ, U.K.
Search for other works by this author on:
Christopher G. PROUD
Christopher G. PROUD
1
*Department of Anatomy and Physiology, University of Dundee, Dundee DD1 4HN, U.K.
1To whom correspondence should be addressed (e-mail CGPROUD@bad.dundee.ac.uk).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
February 05 1998
Revision Received:
May 27 1998
Accepted:
June 23 1998
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1998
1998
Biochem J (1998) 334 (1): 261–267.
Article history
Received:
February 05 1998
Revision Received:
May 27 1998
Accepted:
June 23 1998
Connected Content
A correction has been published:
Amino acid availability regulates p70 S6 kinase and multiple translation factors
Citation
Xuemin WANG, Linda E. CAMPBELL, Christa M. MILLER, Christopher G. PROUD; Amino acid availability regulates p70 S6 kinase and multiple translation factors. Biochem J 15 August 1998; 334 (1): 261–267. doi: https://doi.org/10.1042/bj3340261
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.