The Hsp70 homolog Ssb is essential for glucose sensing via the SNF1 kinase network.

The Hsp70 homolog Ssb is essential for glucose sensing via the SNF1 kinase network.
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Hsp70 同源物 Ssb 对于通过 SNF1 激酶网络进行葡萄糖传感至关重要

DOI:
10.1101/gad.529409
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发表时间:
2009
影响因子:
10.5
通讯作者:
Rospert S
Rospert S
中科院分区:
生物学1区
文献类型:
--
作者:
von Plehwe U;Berndt U;Conz C;Chiabudini M;Fitzke E;Sickmann A;Petersen A;Pfeifer D;Rospert S

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酵母通过多个相互连接的信号网络感知外部能源的可用性。其中一个核心成分是SNF1,它是哺乳动物AMP活化蛋白激酶的同源物,在酵母中对葡萄糖抑制基因的表达至关重要。当葡萄糖可用时,1型蛋白磷酸酶Glc7使过度磷酸化的SNF1失活。去磷酸化需要Reg1,其将Glc7物理靶向SNF1。在这里,我们表明,在葡萄糖的存在下,伴侣蛋白Ssb需要保持SNF1在非磷酸化状态。利用蛋白质组学方法,我们发现Δ ssb 1 Δ ssb 2菌株显示蛋白质表达的改变,并具有葡萄糖阻遏突变体的表型特征。微阵列分析揭示了蛋白质和转录水平的失调之间的相关性。支持性研究发现SSB1是Δ reg1突变引起的严重生长缺陷的有效多拷贝抑制剂。高水平Ssb对Δ reg1的抑制与Snf1过度磷酸化水平降低相关。这些数据与Ssb对于SNF1信号网络内的有效调节至关重要的模型一致,从而允许对葡萄糖水平变化做出适当的响应。
Yeast senses the availability of external energy sources via multiple interconnected signaling networks. One of the central components is SNF1, the homolog of mammalian AMP-activated protein kinase, which in yeast is essential for the expression of glucose-repressed genes. When glucose is available hyperphosphorylated SNF1 is rendered inactive by the type 1 protein phosphatase Glc7. Dephosphorylation requires Reg1, which physically targets Glc7 to SNF1. Here we show that the chaperone Ssb is required to keep SNF1 in the nonphosphorylated state in the presence of glucose. Using a proteome approach we found that the Δssb1Δssb2strain displays alterations in protein expression and suffers from phenotypic characteristics reminiscent of glucose repression mutants. Microarray analysis revealed a correlation between deregulation on the protein and on the transcript level. Supporting studies uncovered thatSSB1was an effective multicopy suppressor of severe growth defects caused by the Δreg1mutation. Suppression of Δreg1by high levels of Ssb was coupled to a reduction of Snf1 hyperphosphorylation back to the wild-type phosphorylation level. The data are consistent with a model in which Ssb is crucial for efficient regulation within the SNF1 signaling network, thereby allowing an appropriate response to changing glucose levels.
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