Identification of cAMP-Dependent Kinase as a Third in Vivo Ribosomal Protein S6 Kinase in Pancreatic β-Cells
Identification of cAMP-Dependent Kinase as a Third in Vivo Ribosomal Protein S6 Kinase in Pancreatic β-Cells
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DOI：
10.1016/j.jmb.2009.04.020
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发表时间：
2009-06-12
影响因子：
5.6
通讯作者：
Herbert, Terence P.
中科院分区：
文献类型：
--
作者：
Moore, Claire E. J.;Xie, Jianling;Herbert, Terence P.
核糖体蛋白S6（rpS 6）在体内被p70 S6蛋白激酶和p90核糖体S6激酶的同种型磷酸化，并且有充分的证据表明其在控制胰腺β细胞大小和功能中起积极作用。在这份报告中，我们证明了在胰腺β细胞系MIN 6（小鼠胰岛素瘤细胞系6）和胰岛，刺激cAMP增加的药物，如胰高血糖素样肽-1和毛喉素，导致rpS 6在Ser 235/Ser 236处的磷酸化，而不依赖于目前已知的体内rpS 6激酶经由对cAMP抑制剂敏感的途径的活化。依赖性蛋白激酶[蛋白激酶A（PKA）]。这种cAMP依赖性rpS 6激酶活性在体外对PKI也敏感，并且PKA在体外仅磷酸化Ser 235/Ser 236上的重组rpS 6。结合这些数据，我们得出结论，PKA可以磷酸化rpS 6只在Ser 235/Ser 236在体内胰腺β细胞，从而提供了一个潜在的重要的cAMP信号转导和蛋白质合成的调节之间的联系。最后，我们提供的证据表明，PKA也可能在体内的Ser 235/Ser 236上磷酸化rpS 6在许多其他哺乳动物细胞类型。(C)2009爱思唯尔有限公司保留所有权利。
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. (C) 2009 Elsevier Ltd. All rights reserved.