Regulation of G2/M progression by the STE mitogen-activated protein kinase pathway in budding yeast filamentous growth
Regulation of G2/M progression by the STE mitogen-activated protein kinase pathway in budding yeast filamentous growth
复制标题
DOI：
10.1091/mbc.10.10.3301
复制
发表时间：
1999-10-01
影响因子：
3.3
通讯作者：
Kron, SJ
中科院分区：
文献类型：
--
作者：
Ahn, SH;Acurio, A;Kron, SJ
将二倍体芽殖酵母接种到贫氮琼脂培养基上刺激MAPK途径以促进丝状生长。丝状细胞的特征包括基因表达的特定模式、细长的细胞形状、极性出芽模式、与母细胞的持续附着以及以G2/M的细胞大小控制为特征的独特细胞周期。虽然丝裂原活化蛋白激酶信号通路在丝状基因表达中的必要性已被充分确立，但该通路在形态发生和细胞周期调控中的作用仍不清楚。我们发现，异位激活的MAPK信号通路诱导细胞周期转移到G2/M协调与其他变化特征的丝状生长。这些作用被酵母有丝分裂细胞周期蛋白Clb 1和Clb 2的过表达所消除。反过来，缺乏Clb 2或携带cdc 28 - 1 N（有丝分裂功能缺陷的CDK等位基因）的酵母显示出增强的丝状分化和对MAPK信号的超敏感性。重要的是，激活Swe 1介导的Cdc 28的Thr-18和/或Tyr-19的抑制性磷酸化并不是MAPK通路影响G2/M延迟所必需的。突变体表达一个nonphosphorylatable突变Cdc 28或缺陷的Swe 1表现出低氮依赖性的丝状生长，并进一步诱导异位MAPK信号。我们推断MAPK通路通过一种新的机制促进丝状生长，该机制抑制有丝分裂细胞周期蛋白/CDK复合物，从而调节细胞形状、出芽模式和细胞-细胞连接。
Inoculation of diploid budding yeast onto nitrogen poor agar media stimulates a MAPK pathway to promote filamentous growth. Characteristics of filamentous cells include a specific pattern of gene expression, elongated cell shape, polar budding pattern, persistent attachment to the mother cell, and a distinct cell cycle characterized by cell size control at G2/M. Although a requirement for MAPK signaling in filamentous gene expression is well established, the role of this pathway in the regulation of morphogenesis al td the cell cycle remains obscure. We find that ectopic activation of the MAPK signal pathway induces a cell cycle shift to G2/M coordinately with other changes characteristic of filamentous growth. These effects are abrogated by overexpression of the yeast mitotic cyclins Clb1 and Clb2. In turn, yeast deficient for Clb2 or carrying cdc28-1N, an allele of CDK defective for mitotic functions, display enhanced filamentous differentiation and supersensitivity to the MAPK signal. Importantly, activation of Swe1-mediated inhibitory phosphorylation of Thr-18 and/or Tyr-19 of Cdc28 is not required for the MAPK pathway to affect the G2/M delay. Mutants expressing a nonphosphorylatable mutant Cdc28 or deficient for Swe1 exhibit low-nitrogen-dependent filamentous growth and are further induced by an ectopic MAPK signal. We infer that the MAPK pathway promotes filamentous growth by a novel mechanism that inhibits mitotic cyclin/CDK complexes and thereby modulates cell shape, budding pattern, and cell-cell connections.