Identification of cAMP-dependent kinase as a third in vivo ribosomal protein S6 kinase in pancreatic beta-cells.
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 beta-cell size and function. In this report, we demonstrate in the pancreatic beta-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 beta-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.
Department of Cell Physiology and Pharmacology, Faculty of Medicine and Biological Sciences, University of Leicester, The Henry Wellcome Building, University Road, Leicester LE1 9HN, UK.
Claire E J
CE
Moore
Jianling
J
Xie
Edith
E
Gomez
Terence P
TP
Herbert
D000818:Animals; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000201:enzymology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051381:Rats; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism
D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D052216:Glucagon-Like Peptide 1; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019893:Ribosomal Protein S6 Kinases; D012694:Serine