Skip Navigation



ToxSci Advance Access published online on September 1, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh273
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
82/2/628    most recent
kfh273v2
kfh273v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Møller, M. T. N.
Right arrow Articles by Seglen, P. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Møller, M. T. N.
Right arrow Articles by Seglen, P. O.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received July 8, 2004
Accepted August 25, 2004

Systems Toxicology

Toxin-Induced Tail Phosphorylation of Hepatocellular S6 Kinase: Evidence for a Dual Involvement of the AMP-Activated Protein Kinase in S6 Kinase Regulation

Michael T. N. Møller 1, Hamid R. Samari 1, Per O. Seglen 1*

1 Proteomics & Mammalian Cell Biology Section, Department of Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway

* To whom correspondence should be addressed. E-mail: p.o.seglen{at}imbv.uio.no.


  Abstract

Several protein phosphatase-inhibitory toxins (okadaic acid, microcystin, calyculin A, cantharidin, tautomycin) administered to isolated rat hepatocytes were found to induce phosphorylation in the tail region of S6 kinase (S6K; p70S6K1) as detected with a phosphospecific antibody against doubly phosphorylated Thr-421/Ser424. AICAR, an adenosine analogue that elicits activation of the hepatocellular AMP-activated protein kinase (AMPK), similarly stimulated S6K tail phosphorylation. The flavonoid naringin prevented the effects of AICAR, okadaic acid and microcystin on AMPK activation as well as on S6K tail phosphorylation, suggesting AMPK as a mediator of the latter. The effects of AICAR and the toxins were rapamycin-resistant; in contrast, amino acids induced an S6K tail phosphorylation that was rapamycin-sensitive, suggesting mediation by the protein kinase mTOR. Amino acids activated S6K by phosphorylation at Thr-389, but the toxins did not, and AICAR in fact suppressed the activating phosphorylation induced by the amino acids. The possibility thus must be considered that the phosphorylated S6K tail may transmit a toxin-induced signal independently of S6K enzymatic activity. Despite their inability to activate S6K, the toxins (but not AICAR) stimulated phosphorylation of the ribosomal protein S6, presumably by activating some other S6-phosphorylating protein kinase.

Keywords: rat; liver; hepatocyte; okadaic acid; microcystin; calyculin A; cantharidin; tautomycin; naringin; AICAR; S6 kinase; AMP-activated protein kinase.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
M. Komatsu, T. Furukawa, R. Ikeda, S. Takumi, Q. Nong, K. Aoyama, S.-i. Akiyama, D. Keppler, and T. Takeuchi
Involvement of Mitogen-Activated Protein Kinase Signaling Pathways in Microcystin-LR-Induced Apoptosis after its Selective Uptake Mediated by OATP1B1 and OATP1B3
Toxicol. Sci., June 1, 2007; 97(2): 407 - 416.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Meley, C. Bauvy, J. H. P. M. Houben-Weerts, P. F. Dubbelhuis, M. T. J. Helmond, P. Codogno, and A. J. Meijer
AMP-activated Protein Kinase and the Regulation of Autophagic Proteolysis
J. Biol. Chem., November 17, 2006; 281(46): 34870 - 34879.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
D. M. Thomson and S. E. Gordon
Impaired overload-induced muscle growth is associated with diminished translational signalling in aged rat fast-twitch skeletal muscle
J. Physiol., July 1, 2006; 574(1): 291 - 305.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.