The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate identification and regulation of cell shape

The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate identification and regulation of cell shape
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DOI:
10.1101/gad.1311105
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发表时间:
2005-07-15
影响因子:
10.5
通讯作者:
Husson, RN
Husson, RN
中科院分区:
生物学1区
文献类型:
--
作者:
Kang, CM;Abbott, DW;Husson, RN

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结核分枝杆菌基因组包含11个丝氨酸/苏氨酸激酶基因,其中包括两个,pounA和pounB,它们是参与细胞形状控制和细胞壁合成的操纵子编码基因的一部分。在这里,我们证明了在指数生长过程中,pKNOAA和PKNOB主要被表达,而这些激酶的过度表达减缓了细胞的生长并改变了细胞的形态。我们确定了PKNOA和PKNOB的首选底物基序,并在体内鉴定了三种底物:PKNOB;细胞分裂蛋白DivIVA的同源基因Wag31;以及功能未知的保守蛋白Rv1422。Wag31的不同等位基因在体内的表达改变了细胞的形状,这种改变取决于产生的蛋白质中的磷受体残基。部分耗尽pounA或pounB会导致细胞变窄、变长。这些数据表明,这些激酶介导的信号转导是调节分枝杆菌细胞形状的一种新机制,这种机制可能在革兰氏阳性细菌中是保守的。
The Mycobacterium tuberculosis genome contains 11 serine/threonine kinase genes including two, pknA and pknB, that are part of an operon encoding genes involved in cell shape control and cell wall synthesis. Here we demonstrate that pknA and pknB are predominantly expressed during exponential growth, and that overexpression of these kinases slows growth and alters cell morphology. We determined the preferred substrate motifs of PknA and PknB, and identified three in vivo substrates of these kinases: PknB; Wag31, an ortholog of the cell division protein DivIVA; and Rv1422, a conserved protein of unknown function. Expression of different alleles of wag31 in vivo alters cell shape, in a manner dependent on the phosphoacceptor residue in the protein produced. Partial depletion of pknA or pknB results in narrow, elongated cells. These data indicate that signal transduction mediated by these kinases is a novel mechanism for the regulation of cell shape in mycobacteria, one that may be conserved among gram-positive bacteria.