AfsR as an integrator of signals that are sensed by multiple serine/threonine kinases in Streptomyces coelicolor A3(2)
AfsR as an integrator of signals that are sensed by multiple serine/threonine kinases in Streptomyces coelicolor A3(2)
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DOI：
10.1007/s10295-003-0063-z
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发表时间：
2003-08-01
影响因子：
3.4
通讯作者：
Horinouchi, S
中科院分区：
文献类型：
--
作者：
Horinouchi, S
天蓝色链霉菌A3（2）的基因组序列揭示了约40种蛋白丝氨酸/苏氨酸或酪氨酸激酶的存在。AfsK能够磷酸化具有ATP酶活性的转录激活因子AfsR，代表了细菌汉克斯型蛋白激酶磷酸化特定蛋白并发挥生物学重要功能的第一个实例。S. coelicolor A3（2）全面控制次生代谢。信号转导途径迄今已证明或建议如下：AfsK松散地附着在膜上，使苏氨酸和丝氨酸残基自磷酸化，可能是在感受到一些外部刺激时，并增强其激酶活性。KbpA是一种AfsK结合蛋白，通过蛋白质-蛋白质相互作用调节激酶活性。激活的AfsK磷酸化细胞质中AfsR的苏氨酸和丝氨酸残基，从而大大增强AfsR的DNA结合活性。除了AfsK，其他激酶-包括PkaG和AfsL-也磷酸化AfsR，这表明AfsR作为这些激酶感知的多个信号的整合器。磷酸化的AfsR结合afsS的启动子，afsS编码63个氨基酸的蛋白质，并与RNA聚合酶形成封闭复合物。封闭的复合物，然后转化为转录活性的开放复合物的能量可从ATP水解的AfsR。以这种方式诱导的AfsS以一种迄今未知的方式激活途径特异性转录激活因子的转录，例如用于放线菌紫素生产的actII-ORF 4和用于十一烷基灵菌红素的redD。
The genome sequence of Streptomyces coelicolor A3(2) has revealed the presence of about 40 protein serine/threonine or tyrosine kinases. AfsK, which is able to phosphorylate AfsR, a transcriptional activator with ATPase activity, represents the first instance in which a bacterial Hanks-type protein kinase phosphorylates a specific protein and exerts biologically important functions. The AfsK-AfsR system in S. coelicolor A3(2) globally controls secondary metabolism. The signal transduction pathway so far demonstrated or suggested is as follows: AfsK loosely attached to the membrane autophosphorylates threonine and serine residues, perhaps on sensing some external stimulus, and enhances its kinase activity. The kinase activity is modulated by KbpA, an AfsK-binding protein, by means of protein-protein interactions. The activated AfsK phosphorylates threonine and serine residues of AfsR in the cytoplasm, by which the DNA-binding activity of AfsR is greatly enhanced. In addition to AfsK, other kinases-including PkaG and AfsL-also phosphorylate AfsR, suggesting that AfsR serves as an integrator of multiple signals sensed by these kinases. The phosphorylated AfsR binds the promoter of afsS, which encodes a protein of 63 amino acids, and forms a closed complex with RNA polymerase. The closed complex is then converted to a transcriptionally active open complex by the energy available from ATP hydrolysis by AfsR. AfsS induced in this way activates transcription of pathway-specific transcriptional activators, such as actII-ORF4 for actinorhodin production and redD for undecylprodigiosin, in an as yet unknown manner.