Protein Tyrosine Phosphatase Inhibitor, Orthovanadate, Induces Contraction via Rho Kinase Activation in Mouse Thoracic Aortas
| Autor: | Yuka Terada, Yuki Hidaka, Naoki Higashi, Katsutoshi Yayama, Yasumasa Isomoto |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pharmacology Myosin light-chain kinase Chemistry Kinase p38 mitogen-activated protein kinases Pharmaceutical Science General Medicine Protein tyrosine phosphatase Molecular biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Phosphorylation Myosin-light-chain phosphatase Rho-associated protein kinase Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Biological and Pharmaceutical Bulletin. 42:877-885 |
| ISSN: | 1347-5215 0918-6158 |
| Popis: | Orthovanadate (OVA), a protein tyrosine phosphatase inhibitor, induces contraction in endothelium-denuded mouse thoracic aortas. OVA-induced contraction was significantly (vs. control rings) suppressed by Rho kinase (Y-27632, 10 µM), extracellular signal-regulated kinase 1 and 2 (Erk1/2, FR180204, 10 µM), Erk1/2 kinase (MEK, PD98059, 10 µM), epidermal growth factor receptor (EGFR, AG1478, 10 µM), and Src inhibitors, and was partially suppressed by c-Jun N-terminal kinase (JNK, AS601245, 10 µM) and p38 (SB203580, 10 µM) inhibitors. However, a myosin light chain kinase inhibitor (ML-7, 10 µM) and a metalloproteinase inhibitor (TAPI-0, 10 µM) had no effect on OVA-induced contraction in mouse thoracic aortas. Phosphorylation of myosin phosphatase target subunit 1 (MYPT1) was abolished by inhibitors of Src, EGFR, MEK, Erk1/2, and Rho kinase, but not by inhibitors of JNK and p38. Erk1/2 phosphorylation by OVA was blocked by inhibitors of EGFR, Src, MEK, and Erk1/2, but not by Rho kinase inhibition. Src phosphorylation at Tyr-416 was abrogated by only Src inhibitor. EGFR phosphorylation at Tyr-1173 was suppressed by a Src inhibitor. These findings suggest that OVA induces contraction via activation of Src, EGFR, MEK, Erk1/2, and Rho kinase, leading to inactivation of myosin light chain phosphatase via MYPT1 phosphorylation. |
| Databáze: | OpenAIRE |
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