論文 - 詳細
| RRC ID | 45023 |
|---|---|
| 著者 | Tsuchiya A, Kanno T, Nagaya H, Shimizu T, Tanaka A, Nishizaki T. |
| タイトル | PTP1B inhibition causes Rac1 activation by enhancing receptor tyrosine kinase signaling. |
| ジャーナル | Cell Physiol Biochem |
| Abstract |
BACKGROUND/AIMS:The present study investigated the signaling pathway underlying Rac1 activation induced by the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA). METHODS:Activity of protein tyrosine phosphatase 1B (PTP1B) was assayed under cell-free conditions. Western blot was carried out to quantify phosphorylation of insulin receptor substrate-1 (IRS-1) and Akt in PC-12 cells. Rac1 activity was monitored in the föerster resonance energy transfer (FRET) analysis using living and fixed PC-12 cells. RESULTS:DCP-LA markedly suppressed PTP1B activity in a concentration (100 pM-100 µM)-dependent manner. In the DCP-LA binding assay, fluorescein-conjugated DCP-LA produced a single fluorescent signal band at 60 kDa, corresponding to the molecule of PTP1B, and the signal was attenuated or abolished by co-treatment or pretreatment with non-conjugated DCP-LA. DCP-LA significantly enhanced nerve growth factor (NGF)-stimulated phosphorylation of IRS-1 at Tyr1222 and Akt1/2 at Thr308/309 and Ser473/474 in PC-12 cells. In the FRET analysis, DCP-LA significantly enhanced NGF-stimulated Rac1 activation, which is abrogated by the phosphatidylinositol 3 kinase (PI3K) inhibitor wortmannin, the 3-phosphoinositide-dependent protein kinase-1 (PDK1) inhibitor BX912, or the Akt inhibitor MK2206. CONCLUSION:The results of the present study show that DCP-LA-induced PTP1B inhibition, possibly through its direct binding, causes Rac1 activation by enhancing a pathway along a receptor tyrosine kinase (RTK)/IRS-1/PI3K/Akt/Rac1 axis. |
| 巻・号 | 33(4) |
| ページ | 1097-105 |
| 公開日 | 2014-1-1 |
| DOI | 10.1159/000358679 |
| PII | 000358679 |
| PMID | 24732916 |
| MeSH | Androstadienes / pharmacology Animals Caprylates / chemistry Caprylates / pharmacology Fluorescein / chemistry Fluorescence Resonance Energy Transfer Heterocyclic Compounds, 3-Ring / pharmacology Insulin Receptor Substrate Proteins / metabolism Nerve Growth Factor / pharmacology PC12 Cells Phosphatidylinositol 3-Kinases / metabolism Phosphorylation / drug effects Protein Serine-Threonine Kinases / metabolism Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism* Proto-Oncogene Proteins c-akt / antagonists & inhibitors Proto-Oncogene Proteins c-akt / metabolism Pyruvate Dehydrogenase Acetyl-Transferring Kinase Rats Receptor, trkA / metabolism* Signal Transduction / drug effects Wortmannin rac1 GTP-Binding Protein / metabolism* |
| IF | 5.5 |
| 引用数 | 5 |
| WOS 分野 | PHYSIOLOGY CELL BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |