Transactivation of EGF receptor induced by G protein-coupled receptor stimulation : the study for signaling cascade by Angiotensin II
| Project/Area Number |
11838019
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Institution | Kansai Medical University |
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Principal Investigator |
MORI Yasukiyo Kansai Medical University, Faculty of Medicine II, Assistant Professor, 医学部, 講師 (40268371)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUBARA Hiraoaki Kansai Medical University, Faculty of Medicine II, Associate Professor, 医学部, 助教授 (10239072)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Vascular smooth muscle / Angiotensin II / Epidermal growth factor / transactivation |
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| Research Abstract |
Transactivation of EGF-receptor induced by AngiotensinII in rat vascular smooth muscle cells and cardiac fibroblasts : Using immunoprecipitation and Western blot analysis, AngII stimulation via type 1 AngII receptor (AT1) was found to phosphorylate EGF-R This phosphorylation was completely abolished by the pretreatment of Ca^<2+> chelating agents, Ca^<2+>/calmodulin inhibitors and tyrosine kinase inhibitors. In addition, specific inhibition of EGF-R by a dominant negative EGF-R mutant and tyrphostin AG1478 abolished the activation of extracellular signal-regulated kinase (ERK) by AT1, leading to the suppression of fibronectin (FN) gene expression by AT1. The promoter analysis using FN-CAT fusion gene revealed that AP-1 binding site was responsible for the AT1 responsiveness of FN gene. G1 retardation assay showed that the pretreatment of AG1478 inhibited AT1-stimulated binding of c-jun and c-fos to AP-1 site in FN gene. In summary, the transactivation of EGF-R induced by angiotensin II is mediated by Ca^<2+>/calmodulin-dependent tyrosine kinases. The activation of ERK and subsequent gene expression such as FN by AT1 were regulated through downstream signaling of EGF-R transactivation.
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Report
(3 results)
Research Products
(2 results)
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[Publications] Hiroaki Matsubara, Yasutaka Moriguchi, Yasukiyo Mori, Hiroya Masaki, Yoshiaki Tsutsumi, Yasunobu Shibasaki, Yoko Uchiyama-Tanaka, soichiro Fujiyama, Atsuko Nose-Fujiyama, Satoshi Iba, Eriko Tateushi and Toshiji Iwasaka: "Transactivation of EGF receptor induced by angiotensin II regulates fibronectin and TGF-β gene expression via transcriptional and post-transcriptional mechanisms"Molecular and Cellular Biochemistry. 212. 187-201 (2000)
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