GSK-3β regulation in skeletal muscles by adrenaline and insulin:: Evidence that PKA and PKB regulate different pools of GSK-3
GSK-3β regulation in skeletal muscles by adrenaline and insulin:: Evidence that PKA and PKB regulate different pools of GSK-3
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DOI：
10.1016/j.cellsig.2006.06.006
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发表时间：
2007-01-01
影响因子：
4.8
通讯作者：
Shepherd, Peter R.
中科院分区：
文献类型：
--
作者：
Jensen, Jorgen;Brennesvik, Erlend O.;Shepherd, Peter R.
我们最近发现，虽然肾上腺素单独对大鼠比目鱼肌中蛋白激酶B(PKB)的激活没有影响，但它极大地增强了胰岛素的作用(Brennesvik等人，Ccell Signating 17：1551-1559,2005)。在目前的研究中，我们继续调查这是否与对PKB的主要靶点GSK-3的类似影响相平行。令人惊讶的是，肾上腺素单独增加了GSK-3βSer(9)和GSK-3αSer(21)的磷酸化，肾上腺素的作用与胰岛素的作用是相加的，但不协同增强胰岛素的作用。二丁酰cAMP(5 MM)和PKA特异性cAMP类似物N-6-苯甲酰cAMP(2 MM)可增加GSK-3βSer(9)的磷酸化，而EPAC特异性cAMP类似物8-(4-氯苯硫基)-2‘-O-甲基-cAMP(1 MM)不能增加GSK-3βSer(9)的磷酸化。Wortmannin可完全阻断胰岛素刺激的GSK-3磷酸化，但在Wortmannin存在的情况下，肾上腺素增加GSK-3βSer(9)的磷酸化。PKA抑制剂H89(50mU M)可降低肾上腺素刺激的GSK-3βSer(9)的磷酸化，但不影响胰岛素的作用。与预期的一样，胰岛素刺激的GSK-3Ser9的磷酸化与GSK-3磷酸化的位点的糖原合成酶的磷酸化降低是平行的。然而，肾上腺素刺激的GSK-3Ser9的磷酸化与糖原合成酶的磷酸化增加是平行的，这表明这一GSK-3池可能不直接参与糖原合成酶的磷酸化。我们的结果表明，比目鱼肌中至少存在两个不同的GSK-3β池，一个被PKA磷酸化，另一个被PKB磷酸化。此外，我们假设这些池中的每一个都参与了不同细胞过程的控制。(C)2006 Elsevier Inc.保留所有权利。
We have recently shown that while adrenaline alone has no effect on the activation of Protein Kinase B (PKB) in rat soleus muscle, it greatly potentiates the effects of insulin (Brennesvik et al., Cellular Signalling 17: 1551-1559, 2005). In the current study we went on to investigate whether this was paralleled by a similar effect on GSK-3, which is a major PKB target. Surprisingly adrenaline alone increased phosphorylation of GSK-3 beta Ser(9) and GSK-3 alpha Ser(21) and adrenaline's effects were additive with those of insulin but did not synergistically potentiate insulin action. Dibutyryl-cAMP (5 mM) and the PKA specific cAMP analogue N-6-Benzoyl-cAMP (2 mM) increased GSK-3 beta Ser(9) phosphorylation, whereas the Epac specific cAMP analogue 8-(4-chlorophenylthio)-2'-O-methyl-cAMP (1 mM) did not. Wortmannin (PI 3-kinase inhibitor; 1 mu M) blocked insulin-stimulated GSK-3 phosphorylation completely, but adrenaline increased GSK-3 beta Ser(9) phosphorylation in the presence of wortmannin. The PKA inhibitor H89 (50 mu M) reduced adrenaline-stimulated GSK-3 beta Ser(9) phosphorylation but did not influence the effects of insulin. Insulin-stimulated GSK-3 Ser9 phosphorylation was paralleled by decreased glycogen synthase phosphorylation at the sites phosphorylated by GSK-3 as expected. However, adrenaline-stimulated GSK-3 Ser9 phosphorylation was paralleled by increased glycogen synthase phosphorylation indicating this pool of GSK-3 may not be directly involved in phosphorylation of glycogen synthase. Our results indicate the existence of at least two distinct pools of GSK-3 beta in soleus muscle, one phosphorylated by PKA and another by PKB. Further, we hypothesise that each of these pools is involved in the control of different cellular processes. (c) 2006 Elsevier Inc. All rights reserved.