Activation of Extracellular-Signal Regulated Kinase by Epidermal Growth Factor Is Potentiated by cAMP-Elevating Agents in Primary Cultures of Adult Rat Hepatocytes
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We investigated the effects of α- and β-adrenergic agonists on epidermal growth factor (EGF)-stimulated extracellular-signal regulated kinase (ERK) isoforms in primary cultures of adult rat hepatocytes. Hepatocytes were isolated and cultured with EGF (20 ng/ml) and/or α1-, α2- and β2-adrenergic agonists. Phosphorylated ERK isoforms (ERK1; p44 mitogen-activated protein kinase (MAPK) and ERK2; p42 MAPK) were detected by Western blotting analysis using anti-phospho-ERK1/2 antibody. The results show that EGF induced a 2.5-fold increase in ERK2-, but not ERK1-, phosphorylation within 3 min. This EGF-induced ERK2 activation was abolished by treatment with the EGF-receptor kinase inhibitor AG1478 (10?7 M) or the MEK (MAPK kinase) inhibitor PD98059 (10?6 M). The α2-adrenergic and β2-adrenergic agonists, UK14304 (10?6 M) and metaproterenol (10?6 M), respectively, had no effect in the absence of EGF, but metaproterenol significantly potentiated EGF-induced ERK2 phosphorylation. Moreover, the cell-permeable cAMP analog 8-bromo cAMP (10?7 M), also potentiated EGF-induced ERK2 phosphorylation. The effects of these analogs were antagonized by the protein kinase A (PKA) inhibitor H-89 (10?7 M). These results suggest that direct or indirect activation of PKA represents a positive regulatory mechanism for EGF stimulation of ERK2 induction.
identifier:JOS-bpb.34.1542
収録刊行物
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 34 (10), 1542-1552, 2011-10
日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1050001202793522176
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- NII論文ID
- 120005352560
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- NII書誌ID
- AA10885497
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- ISSN
- 09186158
- 13475215
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- CiNii Articles