Load-induced focal adhesion kinase activation in the myocardium: role of stretch and contractile activity

PP Domingos, PM Fonseca… - American Journal …, 2002 - journals.physiology.org
PP Domingos, PM Fonseca, W Nadruz Jr, KG Franchini
American Journal of Physiology-Heart and Circulatory Physiology, 2002journals.physiology.org
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∼ 0 to∼ 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 …
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 ∼0 to ∼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.
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