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Synergistic Induction of Mitogen-Activated Protein Kinase Phosphatase-1 by Thrombin and Epidermal Growth Factor Requires Vascular Endothelial Growth Factor Receptor-2
| Content Provider | Scilit |
|---|---|
| Author | Chandrasekharan, Unni M. Waitkus, Matthew Kinney, Corttrell M. Walters-Stewart, Alicia DiCorleto, Paul E. |
| Copyright Year | 2010 |
| Description | Journal: Arteriosclerosis, thrombosis, and vascular biology Objective— To determine the molecular mechanism underlying the synergistic response of mitogen-activated protein kinase phosphatase-1 (MKP-1), which is induced by thrombin and epidermal growth factor (EGF). Methods and Results— MKP-1 induction by thrombin (approximately 6-fold) was synergistically increased (approximately 18-fold) by cotreatment with EGF in cultured endothelial cells. EGF alone did not induce MKP-1 substantially (<2-fold). The synergistic induction of MKP-1 was not mediated by matrix metalloproteinases. The EGF receptor kinase inhibitor AG1478 blocked approximately 70% of MKP-1 induction by thrombin plus EGF (from 18- to 6-fold) but not the response to thrombin alone. An extracellular signal–regulated kinase (ERK)–dependent protease-activated receptor-1 (PAR-1) signal was required for the thrombin alone effect; an ERK-independent PAR-1 signal was necessary for the approximately 12-fold MKP-1 induction by thrombin plus EGF. VEGF induction of MKP-1 was also approximately 12-fold and c-Jun N-terminal kinase (JNK) dependent. Inhibitors of extracellular signal–regulated kinase and JNK activation blocked thrombin plus EGF-induced MKP-1 completely. Furthermore, VEGF receptor 2 depletion blocked the synergistic response without affecting the induction of MKP-1 by thrombin alone. Conclusion— We have identified a novel signaling interaction between protease-activated receptor-1 and EGF receptor that is mediated by VEGF receptor 2 and results in synergistic MKP-1 induction. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956164/pdf https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.110.212399 |
| Ending Page | 1989 |
| Page Count | 7 |
| Starting Page | 1983 |
| ISSN | 10795642 |
| e-ISSN | 15244636 |
| DOI | 10.1161/atvbaha.110.212399 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Issue Number | 10 |
| Volume Number | 30 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2010-10-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Arteriosclerosis, thrombosis, and vascular biology Endocrinology and Metabolism Signal Transduction Vascular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cardiology and Cardiovascular Medicine |
