Ssp1 CaMKK: A Sensor of Actin Polarization That Controls Mitotic Commitment through Srk1 in Schizosaccharomyces pombe.
Ssp1 CaMKK: A Sensor of Actin Polarization That Controls Mitotic Commitment through Srk1 in Schizosaccharomyces pombe.
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DOI：
10.1371/journal.pone.0143037
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Aligue R
中科院分区：
文献类型：
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作者：
Gómez-Hierro A;Lambea E;Giménez-Zaragoza D;López-Avilés S;Yance-Chávez T;Montserrat M;Pujol MJ;Bachs O;Aligue R
钙/钙调蛋白依赖的蛋白激酶(CaMKK)是多种细胞功能所必需的。哺乳动物CaMKK能激活CaMKs，也能激活进化保守的AMP激活蛋白激酶(AMPK)。裂殖酵母CaMKK，Ssp1，是通过AMPK、Ssp2耐受有限葡萄糖和通过SAD激酶Cdr2整合细胞生长和分裂所必需的。在这里，我们报道了Ssp1通过调节CaMK Srk1的活性来控制G2/M转变。我们证明了srk1对CDC25的抑制是由Ssp1调节的；并且通过移除肌动单体结合蛋白孪丝蛋白来恢复ssp1缺失细胞的生长极性和肌动蛋白定位，足以抑制ssp1的表型。这些发现表明，进入有丝分裂是由包括Ssp1和Srk1激酶在内的一系列蛋白质网络介导的。Ssp1将确保适当的极性和细胞大小的组件网络与调节CDK1-Cyclin B活性的蛋白质网络连接起来，其中Ssp1起着抑制作用。
Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is required for diverse cellular functions. Mammalian CaMKK activates CaMKs and also the evolutionarily-conserved AMP-activated protein kinase (AMPK). The fission yeast Schizosaccharomyces pombe CaMKK, Ssp1, is required for tolerance to limited glucose through the AMPK, Ssp2, and for the integration of cell growth and division through the SAD kinase Cdr2. Here we report that Ssp1 controls the G2/M transition by regulating the activity of the CaMK Srk1. We show that inhibition of Cdc25 by Srk1 is regulated by Ssp1; and also that restoring growth polarity and actin localization of ssp1-deleted cells by removing the actin-monomer-binding protein, twinfilin, is sufficient to suppress the ssp1 phenotype. These findings demonstrate that entry into mitosis is mediated by a network of proteins, including the Ssp1 and Srk1 kinases. Ssp1 connects the network of components that ensures proper polarity and cell size with the network of proteins that regulates Cdk1-cyclin B activity, in which Srk1 plays an inhibitory role.