Allosteric regulation of histidine kinases by their cognate response regulator determines cell fate
Allosteric regulation of histidine kinases by their cognate response regulator determines cell fate
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DOI：
10.1016/j.cell.2008.02.045
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发表时间：
2008-05-02
期刊：
影响因子：
64.5
通讯作者：
Jenal, Urs
中科院分区：
文献类型：
--
作者：
Paul, Ralf;Jaeger, Tina;Jenal, Urs
双组分磷酸化网络对细菌的生长和生理至关重要。在这里，我们解决可塑性和互联网内的不同信号转导通路。在新月柄杆菌中，位于相反细胞两极的PleC磷酸酶和DivJ激酶的拮抗活性控制细胞命运决定蛋白DivK的磷酸化状态和亚细胞定位。我们表明，DivK的功能作为一个变构调节开关PleC从磷酸酶到自激酶状态，从而介导了一个循环的二GMP依赖的形态发生程序。通过变构激活DivJ自激酶，DivK也刺激其自身的磷酸化和极性定位。这些数据表明，DivK是一个集成电路的中央效应器，该集成电路通过空间组织的反馈回路来控制C. crescentus。因此，单域响应调节器可以促进串扰、反馈控制和双分量网络的成员之间的远程通信。
The two-component phosphorylation network is of critical importance for bacterial growth and physiology. Here, we address plasticity and interconnection of distinct signal transduction pathways within this network. In Caulobacter crescentus antagonistic activities of the PleC phosphatase and DivJ kinase localized at opposite cell poles control the phosphorylation state and subcellular localization of the cell fate determinator protein DivK. We show that DivK functions as an allosteric regulator that switches PleC from a phosphatase into an autokinase state and thereby mediates a cyclic di-GMP-dependent morphogenetic program. Through allosteric activation of the DivJ autokinase, DivK also stimulates its own phosphorylation and polar localization. These data suggest that DivK is the central effector of an integrated circuit that operates via spatially organized feedback loops to control asymmetry and cell fate determination in C. crescentus. Thus, single domain response regulators can facilitate crosstalk, feedback control, and long-range communication among members of the two-component network.