PMID- 15342961
OWN - NLM
STAT- MEDLINE
DCOM- 20050316
LR  - 20181201
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 82
IP  - 2
DP  - 2004 Dec
TI  - Toxin-induced tail phosphorylation of hepatocellular S6 kinase: evidence for a 
      dual involvement of the AMP-activated protein kinase in S6 kinase regulation.
PG  - 628-37
AB  - 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. 5-Aminoimidazole-4-carboxamide riboside (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 mammalian target 
      of rapamycin (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.
FAU - Moller, Michael T N
AU  - Moller MT
AD  - Proteomics & Mammalian Cell Biology Section, Department of Cell Biology, 
      Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 
      Oslo, Norway.
FAU - Samari, Hamid R
AU  - Samari HR
FAU - Seglen, Per O
AU  - Seglen PO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040901
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Amino Acids)
RN  - 0 (Androstadienes)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Flavanones)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Ribonucleotides)
RN  - 0 (Toxins, Biological)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
RN  - N7TD9J649B (naringin)
RN  - W36ZG6FT64 (Sirolimus)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Amino Acids/pharmacology
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/pharmacology
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology
MH  - Antioxidants/pharmacology
MH  - Blotting, Western
MH  - Cell Separation
MH  - Cyclic AMP-Dependent Protein Kinases/*physiology
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Flavanones/pharmacology
MH  - Gene Expression Regulation, Enzymologic
MH  - Hepatocytes/drug effects/*enzymology
MH  - Immunosuppressive Agents/pharmacology
MH  - In Vitro Techniques
MH  - Indicators and Reagents
MH  - Male
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Wistar
MH  - Ribonucleotides/pharmacology
MH  - Ribosomal Protein S6 Kinases/biosynthesis/*metabolism
MH  - Sirolimus/pharmacology
MH  - Toxins, Biological/*pharmacology
MH  - Wortmannin
EDAT- 2004/09/03 05:00
MHDA- 2005/03/17 09:00
CRDT- 2004/09/03 05:00
PHST- 2004/09/03 05:00 [pubmed]
PHST- 2005/03/17 09:00 [medline]
PHST- 2004/09/03 05:00 [entrez]
AID - kfh273 [pii]
AID - 10.1093/toxsci/kfh273 [doi]
PST - ppublish
SO  - Toxicol Sci. 2004 Dec;82(2):628-37. doi: 10.1093/toxsci/kfh273. Epub 2004 Sep 1.