role of egf receptor transactivation by gpcrs in cardiac hypertrophy
| PAG Title | role of egf receptor transactivation by gpcrs in cardiac hypertrophy |
| PAG ID | WAG001237 |
| Type | P |
| Source Link |  BioCarta |
| Publication Reference | NA |
| PAG Description | One of responses to increased blood pressure is cardiac hypertrophy through increased size of ventricular myocardial cells leading to increased thickness of the ventricular walls. Cardiac hypertrophy allows the heart to handle the increased stress caused by elevated blood pressure but is also a risk factor associated with heart disease. Cardiac hypertrophy results from cross-talk between G-protein coupled receptor sigling and the EGF receptor pathway. Several GPCR ligands are known to stimulate cardiac hypertrophy, including factors that regulate blood pressure such as angiotensin II and endothelin- 1. These factors stimulate phospholipase C through Gq activation, and the production of 1P3 and diacylglycerol second messengers. PKC-delta is activated by DAG and interacts with the metalloproteise ADAM12. ADAM12 cleaves the membrane-bound HB-EGF to release soluble EGF ligand that activates EGF receptor in myocardial cells. EGF receptor activation downstream through small G proteins and the MAP kise pathway ultimately leads to cardiac hypertrophy. Sigls by GPCR ligands such as angiotensin II result in transcriptiol translation of immediate early genes like fos and other genes involved in long-term remodeling of heart tissue and the physiological response to stress in the heart such as the atrial triuretic factor. Factors such as the AKT kise, reactive oxygen species (ROS) and NE-kB also are involved in sigling that leads to hypertrophy, although their role is not yet clear. Blocking this pathway at various steps may prevent heart disease through the prevention of cardiac hypertrophy, but may also have other consequences. |
| Species | Homo sapiens |
| Quality Metric Scores | nCoCo Score: 3,183 |
| Information Content | Rich |
| Other IDs | |
| Base PAG ID | WAG001237 |
| Human Phenotyte Annotation | |
| Curator | PAGER curation team |
| Curator Contact | PAGER-contact@googlegroups.com |
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