Inhibition of SnRK1 by metabolites: Tissue-dependent effects and cooperative inhibition by glucose 1-phosphate in combination with trehalose 6-phosphate
Inhibition of SnRK1 by metabolites: Tissue-dependent effects and cooperative inhibition by glucose 1-phosphate in combination with trehalose 6-phosphate
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DOI：
10.1016/j.plaphy.2012.11.011
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发表时间：
2013-02-01
影响因子：
6.5
通讯作者：
Paul, Matthew J.
中科院分区：
文献类型：
--
作者：
Nunes, Catia;Primavesi, Lucia F.;Paul, Matthew J.
SnRK1属于SNF1/AMPK蛋白激酶家族，是植物体内一种重要的调节蛋白激酶。SnRK1最近被认为是糖信号海藻糖6-磷酸(T6P)的靶标。葡萄糖6-磷酸(G6P)也可以抑制SnRK1，鉴于G6P与T6P在结构上的相似性，我们试图确定它们是否都能对SnRK1产生明显的抑制作用。还检测了其他中枢代谢产物，葡萄糖1-磷酸(G1P)、6-磷酸果糖和UDP-葡萄糖，以及最近报道在小麦籽粒组织中强烈抑制SnRK1的核糖-5-磷酸(R5P)。对于抑制SnRK1的代谢物，动力学模型显示T6P、G1P和G6P各自对SnRK1有明显的调节作用(分别在5.4MU、480MU和1 mM时对SnRK1的抑制作用为50%)。G1P与T6P联合应用对SnRK1有协同抑制作用。与其他抑制剂相比，R5P只抑制绿色组织中的SnRK1。我们表明，这是由于在R5P转化为核酮糖-1，5-二磷酸的过程中，由磷酸核酮酸激酶介导的实验中消耗了ATP。伴随而来的ATP的丧失限制了SnRK1的活性，导致SnRK1的明显抑制。在小麦籽粒制剂中，R5P对SnRK1的抑制可以用绿色果皮组织的存在来解释；这在评估潜在的蛋白激酶抑制剂时暴露了一个重要的警告。数据为代谢产物对SnRK1的调控提供了进一步的见解。Crown版权所有(C)2012，由爱思唯尔·马森公司出版。版权所有。
SnRK1 of the SNF1/AMPK group of protein kinases is an important regulatory protein kinase in plants. SnRK1 was recently shown as a target of the sugar signal, trehalose 6-phosphate (T6P). Glucose 6-phosphate (G6P) can also inhibit SnRK1 and given the similarity in structure to T6P, we sought to establish if each could impart distinct inhibition of SnRK1. Other central metabolites, glucose 1-phosphate (G1P), fructose 6-phosphate and UDP-glucose were also tested, and additionally ribose 5-phosphate (R5P), recently reported to inhibit SnRK1 strongly in wheat grain tissue. For the metabolites that inhibited SnRK1, kinetic models show that T6P, G1P and G6P each provide distinct regulation (50% inhibition of SnRK1 at 5.4 mu M, 480 mu M, >1 mM, respectively). Strikingly, G1P in combination with T6P inhibited SnRK1 synergistically. R5P, in contrast to the other inhibitors, inhibited SnRK1 in green tissues only. We show that this is due to consumption of ATP in the assay mediated by phosphoribulokinase during conversion of R5P to ribulose-1,5-bisphosphate. The accompanying loss of ATP limits the activity of SnRK1 giving rise to an apparent inhibition of SnRK1. Inhibition of SnRK1 by R5P in wheat grain preparations can be explained by the presence of green pericarp tissue; this exposes an important caveat in the assessment of potential protein kinase inhibitors. Data provide further insight into the regulation of SnRK1 by metabolites. Crown Copyright (c) 2012 Published by Elsevier Masson SAS. All rights reserved.