A novel bacterial tyrosine kinase essential for cell division and differentiation
A novel bacterial tyrosine kinase essential for cell division and differentiation
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DOI：
10.1073/pnas.96.23.13068
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发表时间：
1999-11-09
影响因子：
11.1
通讯作者：
Newton, A
中科院分区：
文献类型：
--
作者：
Wu, JG;Ohta, N;Newton, A
蛋白激酶在真核和原核细胞生长、分裂和分化的调节中起核心作用。新月柄杆菌divL基因编码一种对细胞活力和分裂至关重要的新型细菌酪氨酸激酶。虽然DivL蛋白与普遍存在的细菌组氨酸蛋白激酶（HPKs）同源，但它与以前研究的该蛋白激酶家族成员的不同之处在于，它在保守的H盒中含有酪氨酸残基（Tyr-550），而不是组氨酸残基，这是自磷酸化的预期位点。在体外，DivL在Tyr-550上自磷酸化，并且该酪氨酸残基对于细胞活力和细胞分裂周期的调节是必需的。纯化的DivL还催化CtrA的磷酸化并在体外激活细胞周期调节的fliF启动子的转录。ctrA中的抑制突变绕过冷敏感性divL突变体的条件性细胞分裂表型，提供了DivL在细胞周期和发育调节中的功能至少部分由全局反应调节因子CtrA介导的遗传证据。DivL是唯一报道的HPK同源物，其功能已被证明需要酪氨酸上的自磷酸化，因此，它代表了蛋白激酶超家族中的一类新激酶。
Protein kinases play central roles in the regulation of eukaryotic and prokaryotic cell growth, division, and differentiation. The Caulobacter crescentus divL gene encodes a novel bacterial tyrosine kinase essential for cell viability and division. Although the DivL protein is homologous to the ubiquitous bacterial histidine protein kinases (HPKs), it differs from previously studied members of this protein kinase family in that it contains a tyrosine residue (Tyr-550) in the conserved H-box instead of a histidine residue, which is the expected site of autophosphorylation. DivL is autophosphorylated on Tyr-550 in vitro, and this tyrosine residue is essential for cell viability and regulation of the cell division cycle. Purified DivL also catalyzes phosphorylation of CtrA and activates transcription in vitro of the cell cycle-regulated fliF promoter. Suppressor mutations in ctrA bypass the conditional cell division phenotype of cold-sensitive divL mutants, providing genetic evidence that DivL function in cell cycle and developmental regulation is mediated, at least in part, by the global response regulator CtrA. DivL is the only reported HPK homologue whose function has been shown to require autophosphorylation on a tyrosine, and, thus, it represents a new class of kinases within this superfamily of protein kinases.