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