Load-induced focal adhesion kinase activation in the myocardium: role of stretch and contractile activity
Load-induced focal adhesion kinase activation in the myocardium: role of stretch and contractile activity
复制标题
DOI：
10.1152/ajpheart.00534.2001
复制
发表时间：
2002-02-01
影响因子：
4.8
通讯作者：
Franchini, KG
中科院分区：
文献类型：
--
作者：
Domingos, PP;Fonseca, PM;Franchini, KG
我们研究了牵拉和收缩活动对负荷诱导的离体大鼠心脏黏着斑激酶（FAK）和细胞外信号调节激酶（ERK）1/2激活的影响。舒张压从接近0增加到接近15 mmHg迅速增加FAK酪氨酸磷酸化（最大：2.3倍）和与c-Src（最大：2.8倍）和Grb 2（最大：3.6倍）的结合。这被ERK 1/2与FAK的激活（最大值：2.8倍）和结合所抑制。FAK和ERK 1/2的免疫定位在心肌细胞的肌膜位点和细胞核中，在ERK 1/2的情况下。在心脏停搏液灌注的心脏中，球囊膨胀以升高心室压力也激活了FAK和ERK 1/2。然而，增加灌流液中的钙浓度（从0.5至5 mM）诱导的收缩活性的增加并没有激活心肌中的FAK多组分信号传导复合物或ERK 1/2。这些结果表明，拉伸，而不是收缩活动诱导FAK和ERK 1/2激活的心肌。此外，ERK 1/2与FAK的活化和结合表明FAK驱动负荷诱导的ERK 1/2活化。
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 similar to0 to similar to15 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.