論文 - 詳細
| RRC ID | 10777 |
|---|---|
| 著者 | Matsuzawa Y, Kiuchi Y, Toyomura K, Matsumoto I, Nakamura H, Fujino H, Murayama T, Kawashima T. |
| タイトル | Activation of cytosolic phospholipase A2alpha by epidermal growth factor (EGF) and phorbol ester in HeLa cells: different effects of inhibitors for EGF receptor, protein kinase C, Src, and C-Raf. |
| ジャーナル | J Pharmacol Sci |
| Abstract |
In several types of cancer cells, prostaglandins produced via the over-expression of epidermal growth factor receptor (EGFR) and cyclooxygenases regulate cell growth. We investigated the signaling mechanisms for the release of arachidonic acid (AA, a precursor for prostaglandins) in human cervical carcinoma HeLa cells. Treatment with EGF and 4beta-phorbol 12-myristate 13-acetate (PMA) with A23187 released AA accompanied by the phosphorylation of extracellular signal-regulated kinases (ERK1/2). Pharmacological experiments showed that the responses (ERK phosphorylation and AA release) induced by EGF and PMA were mediated by a mitogen-activated protein kinase/ERK kinase (MEK)-ERK-alpha-type cytosolic phospholipase A(2) (cPLA(2)alpha) pathway and that EGFR couples with the pathway in a manner insensitive to sorafenib, an inhibitor of B- and C-Raf, enzymes upstream of MEK. Activation of protein kinase C by PMA couples with the pathway partly in a sorafenib-sensitive and probably C-Raf-mediated manner and partly in a family of Src tyrosine kinases (Src)-dependent and sorafenib-insensitive manner. Co-treatment with sorafenib and an inhibitor of Src family members additionally inhibited the PMA-induced release of AA. Cross-talk between EGFR and protein kinase C was not observed. In human lung carcinoma A549 cells, the release of AA by EGF was insensitive to sorafenib. Possible mechanisms for the sorafenib-insensitive activation of the MEK-ERK-cPLA(2)alpha pathway are discussed. |
| 巻・号 | 111(2) |
| ページ | 182-92 |
| 公開日 | 2009-10-1 |
| DOI | 10.1254/jphs.09201fp |
| PII | JST.JSTAGE/jphs/09201FP |
| PMID | 19783865 |
| MeSH | Benzenesulfonates / pharmacology Cytosol / metabolism Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology* Epidermal Growth Factor / pharmacology* ErbB Receptors / antagonists & inhibitors Group IV Phospholipases A2 / metabolism* HeLa Cells Humans Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Models, Biological Niacinamide / analogs & derivatives Phenylurea Compounds Phosphorylation / drug effects Protein Kinase C / antagonists & inhibitors Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins c-raf / antagonists & inhibitors Pyridines / pharmacology Signal Transduction / drug effects Sorafenib Temperature Tetradecanoylphorbol Acetate / pharmacology* Time Factors src-Family Kinases / antagonists & inhibitors |
| IF | 2.835 |
| 引用数 | 11 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | A549(RCB0098) |