@misc{oai:ir.soken.ac.jp:00000964,
 author = {奉, 龍〓[水+是] and ボン, ヨンシク and BONG, Yong-Sik},
 month = {2016-02-17},
 note = {The Ras GTPase plays a central role in the signal transduction from the cell exterior to the nucleus. These signals elicit very specific cellular responses such as cell proliferation and cell differentiation depending on the stimuli. Fission yeast ras1 plays an important role in two distinctive signal transduction pathways, mating pathway and cytoskeleton organization pathway. The former process occurs upon nutritional stress usually when cells are starved of nitrogen. Cells of two opposite mating types, h<SUP>+</SUP> and h<SUP>-</SUP>, conjugate to produce a diploid zygote, which in turn undergoes meiosis and sporulation, yielding an ascus containing four haploid spores. The ras1 mutant strains are incapable of conjugation and are highly inefficient in sporulation.<br />  Two protein kinases, Byr1 and Byr2 are known to be capable of the partial phenotypic suppression of ras1 mutation. It is known that Ras1 mediates sexual differentiation through the well-conserved MAP kinase pathway composed of Byr2, Byr1, and Spk1 kinase upon nutrient starvation. In addition to the sexual differentiation, Ras1 is involved in cytoskeleton organization. ras1 mutant strains have abnormally round cell morphology compared to rod-shaped morphology of wild type cells. To regulate the organization of the cytoskeleton, Ras 1 interact with Scd1, which is a putative GEF for Cdc42sp, Cdc42sp in turn regulates Shk which is a member of the conserved p21 -activated protein kinase family. In spite of extensive studies on the Ras1-mediated signal transduction pathway, there was no convincing report on factors that could recover the Ras1 function entirely when expressed in ras1 mutant strains. This suggests that Ras1 may be involved in multiple signal transduction pathways that are not revealed yet.<br />   To clarify the ras1 function in fission yeast, it is necessary to understand overallview of genes regulated by Ras1 mediated signaling pathway; to know the ras1 function clearly in fission yeast, the DNA microarray containing 13,824 S. pombe genomic clones was prepared. Using this DNA chip, the author screened differentially-expressed genes between ras1 mutant and wild type cells. Total of 305 clones was identified to show over 2-fold increase or decrease. Among them, the author selected 38 clones that showed 2.5-fold of increase or decrease. The author analyzed several characteristics of these clones to know function related to their expression.<br />   First, in ras1 mutant cells, the factors controlling ion transport were increased compared to that of wild type cells (ferric reductase, calcium permease, and sodium ion / proton antiporter). This result may imply that factors related to the ion transport or homeostasis are under the control of RasGTPase signaling pathway. Second, the factors related to the stress response were also increased in ras1 mutant cells (putative sensory transduction histidine kinase and longevity assurance factor). Third, transcription factor whose function is unknown was also increased in ras1 mutant cells.<br />   It was reported that the transcription factor AFT1 controlling gene expression of ferric reductase was involved in cell size control in S. cerevisiae. For this reason, the author focused his attention on gene coding for ferric reductase that was increased in ras1 mutant cells. Through the northern blot analysis, the author confirmed that the expression of genes coding for ferric reductase was increased in ras1 mutant cell. A ferric reductase in S. cerevisiae, is involved in uptake of iron and copper ions.<br />   The author thought that ras1 mutant cells would be resistant against starvation of iron and copper ion and this fact was verified through the starvation experiment of iron and copper ion. This result suggests that ras1 mutant cells are resistant against to iron and copper ion starvation compared to that of wild type cell. Increased expression of ferric reductase is related to the resistance to iron and copper starvation. In fission yeast, the mutant for ion homeostasis has the defect in cell wall integrity. It was revealed that Ras1 mutant cells are sensitive to treatment of cell wall lysis enzyme through the β-glucanase sensitivity experiment. This result suggests that cell wall composition of ras1 mutant cell is changed compared to that of wild cells.<br />   Taken together, this study suggests that Ras1 might involved in signaling pathway controlling cell wall integrity and ion homeostasis as well as mating and cytoskeleton in fission yeast. In this study, the author described the identification and characterization of genes that are regulated by RasGTPase in fission yeast., 総研大甲第555号},
 title = {Identification and characterization of genes which are regulated by Ras GTPase-mediated signal transduction pathway in Schizosaccharomyces pombe.},
 year = {}
}