RGD Reference Report - Ribosomal protein S6 phosphorylation and function during late gestation liver development in the rat. - Rat Genome Database

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Ribosomal protein S6 phosphorylation and function during late gestation liver development in the rat.

Authors: Boylan, JM  Anand, P  Gruppuso, PA 
Citation: Boylan JM, etal., J Biol Chem. 2001 Nov 30;276(48):44457-63. Epub 2001 Sep 26.
RGD ID: 1626103
Pubmed: PMID:11574531   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M103457200   (Journal Full-text)

The phosphorylation of ribosomal protein S6 is thought to be required for biosynthesis of the cell's translational apparatus, a critical component of cell growth and proliferation. We have studied the signal transduction pathways involved in hepatic S6 phosphorylation during late gestation in the rat. This is a period during which hepatocytes show a high rate of proliferation that is, at least in part, independent of mitogenic signaling pathways that are operative in mature hepatocytes. Our initial studies demonstrated that there was low basal activity of two S6 kinases in liver, S6K1 and S6K2, on embryonic day 19 (2 days preterm). In addition, insulin- and growth factor-mediated S6K1 and S6K2 activation was markedly attenuated compared with that in adult liver. Nonetheless, two-dimensional gel electrophoresis demonstrated that fetal liver S6 itself was highly phosphorylated. To characterize the fetal hepatocyte pathway for S6 phosphorylation, we went on to study the sensitivity of hepatocyte proliferation to the S6 kinase inhibitor rapamycin. Unexpectedly, administration of rapamycin to embryonic day 19 fetuses in situ did not affect hepatocyte DNA synthesis. This resistance to the growth inhibitory effect of rapamycin occurred even though S6K1 and S6K2 were inhibited. Furthermore, fetal hepatocyte proliferation was sustained even though rapamycin administration resulted in the dephosphorylation of ribosomal protein S6. In contrast, rapamycin blocked hepatic DNA synthesis in adult rats following partial hepatectomy coincident with S6 dephosphorylation. We conclude that hepatocyte proliferation in the late gestation fetus is supported by a rapamycin-resistant mechanism that can function independently of ribosomal protein S6 phosphorylation.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein phosphorylation  IDA 1626103; 1626103 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ATP binding  IDA 1626103; 1626103 RGD 
peptide binding  IDA 1626103; 1626103 RGD 
protein kinase activity  IDA 1626103; 1626103 RGD 
ribosomal protein S6 kinase activity  IMP 1626103; 1626103 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mTOR signaling pathway   IMP 1626103; 1626103 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Rps6kb1  (ribosomal protein S6 kinase B1)
Rps6kb2  (ribosomal protein S6 kinase B2)


Additional Information