German Cancer Research Center, DKFZ-ZMBH Alliance, Molecular Biology of Centrosomes and Cilia, 69120 Heidelberg, Germany.
J Cell Biol. 2010 Sep 20;190(6):975-89. doi: 10.1083/jcb.201006151.
Budding yeast asymmetric cell division relies upon the precise coordination of spindle orientation and cell cycle progression. The spindle position checkpoint (SPOC) is a surveillance mechanism that prevents cells with misoriented spindles from exiting mitosis. The cortical kinase Kin4 acts near the top of this network. How Kin4 kinase activity is regulated and maintained in respect to spindle positional cues remains to be established. Here, we show that the bud neck-associated kinase Elm1 participates in Kin4 activation and SPOC signaling by phosphorylating a conserved residue within the activation loop of Kin4. Blocking Elm1 function abolishes Kin4 kinase activity in vivo and eliminates the SPOC response to spindle misalignment. These findings establish a novel function for Elm1 in the coordination of spindle positioning with cell cycle progression via its control of Kin4.
芽殖酵母不对称细胞分裂依赖于纺锤体取向和细胞周期进程的精确协调。纺锤体位置检查点（SPOC）是一种监控机制，可防止纺锤体取向错误的细胞退出有丝分裂。皮质激酶 Kin4 在该网络的顶部附近起作用。激酶活性如何针对纺锤体位置线索进行调节和维持仍有待确定。在这里，我们表明与芽颈相关的激酶 Elm1 通过磷酸化 Kin4 的激活环中的保守残基参与 Kin4 的激活和 SPOC 信号传导。阻断 Elm1 的功能会在体内消除 Kin4 的激酶活性，并消除纺锤体错位对 SPOC 反应。这些发现为 Elm1 通过控制 Kin4 来协调纺锤体定位与细胞周期进程提供了一个新的功能。
