McCusker Derek, Denison Carilee, Anderson Scott, Egelhofer Thea A, Yates John R, Gygi Steven P, Kellogg Douglas R
Department of Molecular, Cell and Developmental Biology, University of California, 1156 High Street, Santa Cruz, CA 95064, USA.
Nat Cell Biol. 2007 May;9(5):506-15. doi: 10.1038/ncb1568. Epub 2007 Apr 8.
The mechanisms that control cell growth during the cell cycle are poorly understood. In budding yeast, cyclin dependent kinase 1 (Cdk1) triggers polarization of the actin cytoskeleton and bud emergence in late G1 through activation of the Cdc42 GTPase. However, Cdk1 is not thought to be required for subsequent growth of the bud. Here, we show that Cdk1 has an unexpected role in controlling bud growth after bud emergence. Moreover, we show that G1 cyclin-Cdk1 complexes specifically phosphorylate multiple proteins associated with Cdc24, the guanine nucleotide-exchange factor (GEF) that activates the Cdc42 GTPase. A mutant form of a Cdc24-associated protein that fails to undergo Cdk1-dependent phosphorylation causes defects in bud growth. These results provide a direct link between Cdk1 activity and the control of polarized cell growth.
在细胞周期中控制细胞生长的机制仍知之甚少。在芽殖酵母中，细胞周期蛋白依赖性激酶1（Cdk1）通过激活Cdc42 GTP酶在G1晚期触发肌动蛋白细胞骨架的极化和芽的出现。然而，Cdk1被认为不是芽随后生长所必需的。在这里，我们表明Cdk1在芽出现后控制芽生长方面具有意想不到的作用。此外，我们表明G1细胞周期蛋白-Cdk1复合物特异性地磷酸化与Cdc24相关的多种蛋白质，Cdc24是激活Cdc42 GTP酶的鸟嘌呤核苷酸交换因子（GEF）。一种与Cdc24相关的蛋白质的突变形式，其不能进行依赖Cdk1的磷酸化，会导致芽生长缺陷。这些结果提供了Cdk1活性与极化细胞生长控制之间的直接联系。
