5'-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2A(c)
5'-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2A(c)
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DOI：
10.1016/0014-5793(95)01368-7
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发表时间：
1995-12-27
期刊：
影响因子：
3.5
通讯作者：
Hardie, DG
中科院分区：
文献类型：
--
作者：
Davies, SP;Helps, NR;Hardie, DG
人蛋白磷酸酶 - 2Cα（PP2Cα）在大肠杆菌中表达后被纯化至同质。腺苷一磷酸（AMP）抑制PP2Cα对腺苷酸活化蛋白激酶（AMPK）的去磷酸化作用，但不抑制对磷酸酪蛋白的去磷酸化作用。浓度依赖性以及其他核苷酸（三磷酸腺苷和间型霉素A - 5'-单磷酸）的影响表明，AMP通过与引起AMPK直接别构激活的同一部位结合而发挥作用。在另一种蛋白磷酸酶（PP2A(C)）中观察到了一种类似但不太明显的效应。我们现在已经表明，AMPK通过四种机制激活AMPK级联反应，这应该使该系统对AMP浓度的变化极为敏感。
Human protein phosphatase-2C alpha (PP2C alpha) was purified to homogeneity after expression in Escherichia coli, AMP inhibited the dephosphorylation of AMP-activated protein kinase (AMPK), but not phosphocasein, by PP2C alpha. The concentration dependence and the effects of other nucleotides (ATP and formycin A-5'-monophosphate) suggest that AMP acts by binding to the same site which causes direct allosteric activation of AMPK, A similar, although less pronounced, effect was observed with another protein phosphatase (PP2A(C)). We have now shown that AMPK activates the AMPK cascade by four mechanisms, which should make the system exquisitely sensitive to changes in AMP concentration.