Departamento Ciencias Biomédicas, Universidad de Extremadura, 06071 Badajoz, Spain.
Mol Biol Cell. 2011 Jul 15;22(14):2458-69. doi: 10.1091/mbc.E11-03-0205. Epub 2011 May 18.
Nuclear Dbf2-related (NDR) protein kinases are essential components of regulatory pathways involved in cell morphogenesis, cell cycle control, and viability in eukaryotic cells. For their activity and function, these kinases require interaction with Mob proteins. However, little is known about how the Mob proteins are regulated. In Candida albicans, the cyclin-dependent kinase (CDK) Cdc28 and the NDR kinase Cbk1 are required for hyphal growth. Here we demonstrate that Mob2, the Cbk1 activator, undergoes a Cdc28-dependent differential phosphorylation on hyphal induction. Mutations in the four CDK consensus sites in Mob2 to Ala significantly impaired hyphal development. The mutant cells produced short hyphae with enlarged tips that displayed an illicit activation of cell separation. We also show that Cdc28 phosphorylation of Mob2 is essential for the maintenance of polarisome components at hyphal tips but not at bud tips during yeast growth. Thus we have found a novel signaling pathway by which Cdc28 controls Cbk1 through the regulatory phosphorylation of Mob2, which is crucial for normal hyphal development.
核 Dbf2 相关（NDR）蛋白激酶是真核细胞中参与细胞形态发生、细胞周期控制和存活的调节途径的重要组成部分。为了发挥其活性和功能，这些激酶需要与 Mob 蛋白相互作用。然而，关于 Mob 蛋白如何被调控的知识却知之甚少。在白色念珠菌中，细胞周期蛋白依赖性激酶（CDK）Cdc28 和 NDR 激酶 Cbk1 是菌丝生长所必需的。在这里，我们证明了 Cbk1 的激活剂 Mob2 在菌丝诱导时经历了 Cdc28 依赖性的差异磷酸化。Mob2 中四个 CDK 共有序列突变为 Ala 显著削弱了菌丝的发育。突变细胞产生了短的菌丝，其顶端扩大，显示出细胞分离的非法激活。我们还表明，Mob2 的 Cdc28 磷酸化对于维持菌丝顶端极体成分是必不可少的，但在酵母生长过程中对于芽顶端则不是必需的。因此，我们发现了一条新的信号通路，Cdc28 通过对 Mob2 的调节性磷酸化来控制 Cbk1，这对于正常的菌丝发育至关重要。
