Key role of ERK1/2 molecular scaffolds in heart pathology
| Autor: | Guido Tarone, Mauro Sbroggiò, Mara Brancaccio |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Scaffold protein
Arrestins MAP Kinase Signaling System Biology Mice Cellular and Molecular Neuroscience GTP-Binding Protein gamma Subunits Animals Humans Myocytes Cardiac Phosphorylation Molecular Biology beta-Arrestins Heart Failure Pharmacology Kinase Beta-Arrestins Effector Myocardium GTP-Binding Protein beta Subunits Heart Cell Biology Adaptive response Hedgehog signaling pathway Protein Structure Tertiary Cell biology Signalling Molecular Medicine raf Kinases Signal transduction Signal Transduction |
| Zdroj: | Cellular and Molecular Life Sciences. 70:4047-4054 |
| ISSN: | 1420-9071 1420-682X |
| Popis: | The ability of cardiomyocytes to detect mechanical and humoral stimuli is critical for adaptation of the myocardium in response to new conditions and for sustaining the increased workload during stress. While certain stimuli mediate a beneficial adaptation to stress conditions, others result in maladaptive remodelling, ultimately leading to heart failure. Specific signalling pathways activating either adaptive or maladaptive cardiac remodelling have been identified. Paradoxically, however, in a number of cases, the transduction pathways involved in such opposing responses engage the same signalling proteins. A notable example is the Raf-MEK1/2-ERK1/2 signalling pathway that can control both adaptive and maladaptive remodelling. ERK1/2 signalling requires a signalosome complex where a scaffold protein drives the assembly of these three kinases into a linear pathway to facilitate their sequential phosphorylation, ultimately targeting specific effector molecules. Interestingly, a number of different Raf-MEK1/2-ERK1/2 scaffold proteins have been identified, and their role in determining the adaptive or maladaptive cardiac remodelling is a promising field of investigation for the development of therapeutic strategies capable of selectively potentiating the adaptive response. |
| Databáze: | OpenAIRE |
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