Screening of Drugs That Suppress Ste11 MAPKKK Activation in Yeast Identified a c-Abl Tyrosine Kinase Inhibitor
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概要
- 論文の詳細を見る
The yeast MAPKKK Ste11 activates three MAP kinase pathways, including pheromone signaling, osmosensing, and pseudohyphal/invasive growth pathways. We identified two chemical compounds, BTB03006 and GK03225, that suppress growth defects induced by Ste11 activation in diploid yeast cells. BTB03006, but not GK03225, was found to suppress growth defects induced by both α-factor and Ste4 Gβ overexpression in the pheromone signaling pathway, suggesting that GK03225 is an osmosensing pathway-specific inhibitor. We also performed genome-wide suppressor analysis for Ste11 activation, using a yeast deletion strains collection, and identified PBS2 and HOG1, and several genes associated with chaperone functions, which represent potential target proteins of the drugs screened from Ste11 activation. GK03225 possesses an Iressa-like quinazoline ring structure, and its chemical analog, 11N-078, suppresses c-Abl human tyrosine kinase activity. These results suggest that drug screening in yeast can identify human tyrosine kinase inhibitors and other drugs for human diseases.
- 社団法人 日本農芸化学会の論文
- 2007-03-23
著者
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TAKAHASHI Hidetoshi
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd.
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HOSHIDA Hisashi
Department of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine
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AKADA Rinji
Department of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine
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Akada Rinji
Department Of Applied Chemistry And Chemical Engineering Faculty Of Engineering Yamaguchi University
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Hoshida Hisashi
Department Of Applied Chemistry And Chemical Engineering Faculty Of Engineering Yamaguchi University
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UCHIDA Motoyuki
Biomedical Research Laboratories, Kureha Chemical Industry Co.
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FUJIEDA Ayako
Biomedical Research Laboratories, Kureha Corporation
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Fujieda Ayako
Biomedical Research Laboratories Kureha Corporation
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Uchida Motoyuki
Biomedical Research Laboratories Kureha Chemical Industry Co. Ltd.
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Kitagawa Takao
Department Of Applied Molecular Bioscience Yamaguchi University Graduate School Of Medicine
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HASHIZUME Yuko
Department of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine
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MURAKANE Tatsuhiko
Department of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine
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KOGA Emi
Department of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine
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NOMURA Yuki
Department of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine
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KAKIHARA Yoshito
Department of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine
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Hoshida Hisashi
Department Of Applied Molecular Bioscience Yamaguchi University Graduate School Of Medicine
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Koga Emi
Department Of Applied Molecular Bioscience Yamaguchi University Graduate School Of Medicine
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Nomura Yuki
Graduate School Of Biological Sciences Nara Inst. Of Sci. And Technol. (naist)
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Nomura Yuki
Department Of Anesthesiology Sumitomo Hospital
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Hashizume Yuko
Department Of Applied Molecular Bioscience Yamaguchi University Graduate School Of Medicine
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Kakihara Yoshito
Department Of Applied Molecular Bioscience Yamaguchi University Graduate School Of Medicine
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Takahashi Hidetoshi
Research Institute Of Life Science Snow Brand Milk Products Co. Ltd.
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Murakane Tatsuhiko
Department Of Applied Molecular Bioscience Yamaguchi University Graduate School Of Medicine
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UCHIDA Motoyuki
Biomedical Research Laboratories, Kureha Corporation
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NOMURA Yuki
Department of Anesthesiology and Perioperative Medicine, Kobe University Graduate School of Medicine
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