Stretch induced by increasing diastolic pressure to ~15 mmHg rapidly increased FAK tyrosine phosphorylation by up to 2.3-fold in isolated rat hearts, whereas increased contractile activity did not.
Mechanical stretch, rather than contractile activity, induces FAK and ERK1/2 activation in the myocardium, suggesting FAK drives load-induced ERK1/2 activation.
Effect estimate: 2.3-fold increase
We investigated the influence of stretch and contractile activity on load-induced activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK)1/2 in isolated rat hearts. Increases of diastolic pressure from approximately 0 to approximately 15 mmHg rapidly increased FAK tyrosine phosphorylation (maximum: 2.3-fold) and binding to c-Src (maximum: 2.8-fold) and Grb2 (maximum: 3.6-fold). This was paralleled by activation (maximum: 2.8-fold) and binding of ERK1/2 to FAK. FAK and ERK1/2 were immunolocalized at sarcolemmal sites of cardiac myocytes and in the nuclei, in the case of ERK1/2. Balloon inflation to raise ventricular pressure in hearts perfused with cardioplegic solution also activated FAK and ERK1/2. However, increases in contractile activity induced by increasing calcium concentration in the perfusate (from 0.5 to 5 mM) did not activate the FAK multicomponent signaling complex or ERK1/2 in the myocardium. These results indicate that stretch rather than contractile activity induces FAK and ERK1/2 activation in the myocardium. In addition, the activation and binding of ERK1/2 to FAK suggest that FAK drives the load-induced activation of ERK1/2.
Domingos et al. (Fri,) conducted a other in Isolated rat hearts. Stretch (increased diastolic pressure) vs. Contractile activity (increased calcium concentration) was evaluated on FAK tyrosine phosphorylation and binding to c-Src and Grb2 (2.3-fold increase). Stretch induced by increasing diastolic pressure to ~15 mmHg rapidly increased FAK tyrosine phosphorylation by up to 2.3-fold in isolated rat hearts, whereas increased contractile activity did not.