Watanabe Y, Takaesu G, Hagiwara M, Irie K, Matsumoto K
Department of Molecular Biology, Faculty of Science, Nagoya University, Chikusa-ku, Japan.
Mol Cell Biol. 1997 May;17(5):2615-23. doi: 10.1128/MCB.17.5.2615.
The Mpk1 (Slt2) mitogen-activated protein (MAP) kinase has been implicated in several biological processes in Saccharomyces cerevisiae. The Rlm1 protein, a member of the MADS box family of transcription factors, functions downstream of Mpk1 in the pathway. To characterize the role of Rlm1 in mediating the transcriptional activation by the Mpk1 pathway, we constructed a LexA-Rlm1 deltaN chimera in which sequences, including the MADS box domain of the Rlm1 protein, were replaced by the LexA DNA binding domain and tested the ability of this chimera to activate a LexA operator-controlled reporter gene. In this assay, the Rlm1 protein was found to activate transcription in a manner regulated by the Mpk1 pathway. The Mpk1 protein kinase phosphorylated Rlm1 deltaN in vitro and the LexA-Rlm1 deltaN chimera protein was phosphorylated in vivo in a Mpk1-dependent manner. These results suggest that Mpk1 regulates the transcriptional activity of Rlm1 by directly phosphorylating it. We identified a Mpk1-like protein kinase, Mlp1, as an Rlm1-associated protein by using the yeast two-hybrid system. Overexpression of MLP1 suppresses the caffeine-sensitive phenotype of the bck1 delta mutation. The additivity of the mlp1 delta defect with the Mpk1 delta defect with regard to the caffeine sensitivity, combined with the results of genetic epistasis experiments, suggested that the activity of Rlm1 is regulated independently by Mpk1 MAP kinase and the Mlp1 MAP kinase-like kinase.
Mpk1(Slt2)丝裂原活化蛋白(MAP)激酶参与了酿酒酵母中的多个生物学过程。Rlm1蛋白是转录因子MADS盒家族的成员,在该途径中位于Mpk1的下游发挥作用。为了表征Rlm1在介导Mpk1途径的转录激活中的作用,我们构建了一个LexA-Rlm1 deltaN嵌合体,其中包括Rlm1蛋白的MADS盒结构域在内的序列被LexA DNA结合结构域取代,并测试了该嵌合体激活LexA操纵子控制的报告基因的能力。在该实验中,发现Rlm1蛋白以受Mpk1途径调节的方式激活转录。Mpk1蛋白激酶在体外使Rlm1 deltaN磷酸化,并且LexA-Rlm1 deltaN嵌合体蛋白在体内以Mpk1依赖的方式被磷酸化。这些结果表明,Mpk1通过直接磷酸化来调节Rlm1的转录活性。我们使用酵母双杂交系统鉴定出一种Mpk1样蛋白激酶Mlp1作为与Rlm1相关的蛋白。MLP1的过表达抑制了bck1 delta突变的咖啡因敏感表型。mlp1 delta缺陷与Mpk1 delta缺陷在咖啡因敏感性方面的累加性,结合遗传上位性实验的结果,表明Rlm1的活性由Mpk1 MAP激酶和Mlp1 MAP激酶样激酶独立调节。