RGD Reference Report - Toxin-induced tail phosphorylation of hepatocellular S6 kinase: evidence for a dual involvement of the AMP-activated protein kinase in S6 kinase regulation. - Rat Genome Database

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Toxin-induced tail phosphorylation of hepatocellular S6 kinase: evidence for a dual involvement of the AMP-activated protein kinase in S6 kinase regulation.

Authors: Moller, MT  Samari, HR  Seglen, PO 
Citation: Moller MT, etal., Toxicol Sci. 2004 Dec;82(2):628-37. Epub 2004 Sep 1.
RGD ID: 1643036
Pubmed: PMID:15342961   (View Abstract at PubMed)
DOI: DOI:10.1093/toxsci/kfh273   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to toxic substance  IEP 1643036 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rps6kb1  (ribosomal protein S6 kinase B1)


Additional Information