Effect of Herbimycin A on Tyrosine Kinase Receptors and Platelet Derived Growth Factor (PDGF)-Induced Signal Transduction
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概要
- 論文の詳細を見る
Herbimycin A is widely used as an inhibitor of Src family protein tyrosine kinases but is also reported to induce the downregulation of epidermal growth factor (EGF) receptor number in A431 cells without inhibiting its tyrosine kinase activity. To determine the specificity of the receptor downregulation, we examined its effect on a variety of cell lines which express different levels of EGF receptor and on other tyrosine kinase receptors. Longterm herbimycin A treatment decreased the amounts of all the tyrosine kinase receptors examined in a dose-dependent manner. It also reduced ligand-stimulated receptor autophosphorylation in accordance with the reduction in the receptor level. Herbimycin A inhibited platelet derived growth factor (PDGF)-induced tyrosine phosphorylation of cellular proteins and DNA synthesis in NIH3T3 cells but did not affect the serum-stimulated DNA synthesis. PDGF-induced tyrosine phosphorylation and activation of c-Src was inhibited but the protein level of c-Src was not reduced by herbimycin A. The reduced level of c-Src kinase activity correlated with the levels of both PDGF receptor and DNA synthesis. These results indicate that the herbimycin A treatment selectively downregulates receptor tyrosine kinases, independent of the number of receptors, and suggest that c-Src is to some degree involved in the selective inhibition of PDGF-induced mitogenesis by herbimycin A.
- 公益社団法人日本薬学会の論文
- 1998-10-15
著者
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MURAKAMI Yuko
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University
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Murakami Yukihisa
富山大学和漢医薬学総合研究所 複合薬物薬理学
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Mukarami Yukihisa
Institute Of Natural Medicine Toyama Medical And Pharmaceutical University
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Murakami Yukihisa
Division Of Medicinal Pharmacology Institute Of Natural Medicine Toyama Medical And Pharmaceutical U
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Murakami Yukihisa
Research Institute For Wakan-yaku (traditional Sino-japanese Medicines)
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UEHARA Yoshimasa
Department of Bioactive Molecules, National Institute of Infectious Diseases
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Murakami Yuko
Deparment Of Radiology Dokkyo University School Of Medicine Koshigaya Hospital
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FUKAZAWA Hidesuke
Department of Bioactive Molecules, National Institute of Infectious Diseases
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Uehara Yoshimasa
Department Of Bioactive Molecules National Institute Of Infectious Diseases
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Murakami Y
Department Of Bioactive Molecules National Institute Of Infectious Diseases
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MIZUNO Satoshi
Department of Bioactive Molecules, National Institute of Health
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Mizuno Satoshi
アール・ピー・シーラー株式会社学術課
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Mizuno S
Department Of Bioactive Molecules National Institute Of Infectious Diseases
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Mizuno Satoshi
Department Of Bioactive Molecules National Institute Of Infectious Diseases
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Mizuno S
アール・ピー・シーラー株式会社学術課
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Fukazawa H
Department Of Bioactive Molecules National Institute Of Infectious Diseases
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