Identification of cAMP-Dependent Kinase as a Third in Vivo Ribosomal Protein S6 Kinase in Pancreatic β-Cells

Claire E.J. Moore, Jianling Xie, Edith Gomez, Terence P. Herbert

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45 Citations (Scopus)


Ribosomal protein S6 (rpS6) is phosphorylated in vivo by isoforms of p70 S6 protein kinase and p90 ribosomal S6 kinase, and there is good evidence that it plays a positive role in controlling pancreatic β-cell size and function. In this report, we demonstrate in the pancreatic β-cell line MIN6 (mouse insulinoma cell line 6) and islets of Langerhans that agents which stimulate increases in cAMP, such as glucagon-like peptide-1 and forskolin, lead to the phosphorylation of rpS6 at Ser235/Ser236 independently of the activation of the currently known in vivo rpS6 kinases via a pathway that is sensitive to inhibitors of cAMP-dependent protein kinase [protein kinase A (PKA)]. This cAMP-dependent rpS6 kinase activity is also sensitive to PKI in vitro, and PKA exclusively phosphorylates recombinant rpS6 on Ser235/Ser236 in vitro. With these data taken together, we conclude that PKA can phosphorylate rpS6 exclusively at Ser235/Ser236 in vivo in pancreatic β-cells, thus providing a potentially important link between cAMP signalling and the regulation of protein synthesis. Lastly, we provide evidence that PKA is also likely to phosphorylate rpS6 on Ser235/Ser236 in vivo in a number of other mammalian cell types.

Original languageEnglish
Pages (from-to)480-494
Number of pages15
JournalJournal of Molecular Biology
Issue number3
Publication statusPublished or Issued - 12 Jun 2009
Externally publishedYes


  • GLP1
  • PKA
  • S6K
  • mTORC1
  • rpS6

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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