PKCepsilon-PKD1 signaling complex at Z-discs plays a pivotal role in the cardiac hypertrophy induced by G-protein coupling receptor agonists.
PKCepsilon-PKD1 signaling complex at Z-discs plays a pivotal role in the cardiac hypertrophy induced by G-protein coupling receptor agonists.
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DOI：
10.1016/j.bbrc.2004.12.128
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发表时间：
2005-02
影响因子：
3.1
通讯作者：
Miki Iwata;A. Maturana;M. Hoshijima;K. Tatematsu;T. Okajima;J. Vandenheede;J. Van Lint;K. Tanizawa;S. Kuroda
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文献类型：
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作者：
Miki Iwata;A. Maturana;M. Hoshijima;K. Tatematsu;T. Okajima;J. Vandenheede;J. Van Lint;K. Tanizawa;S. Kuroda
心肌肥大是由机械应力和各种神经体液因子，如G蛋白偶联受体（GPCR）和gp 130细胞因子受体激动剂引起的。最近的研究表明，心脏Z盘在调节这些细胞反应中起着关键作用。在这里，我们证明刺激与GPCR激动剂（去甲肾上腺素，血管紧张素II，内皮素1）和佛波酯激活和易位蛋白激酶D1（PKD 1）的Z-盘在新生大鼠心肌细胞中的蛋白激酶C（PKC）依赖的方式，而gp 130激动剂没有。特别是在α-肾上腺素能受体激动剂刺激下，PKCε-PKD 1复合物形成后，PKCε依赖性激活PKD 1是诱导肥大反应的必要条件。PKD 1或PKCε的组成性活性突变体也诱导离体心肌肥大。因此，Z盘上的PKCε-PKD 1复合物可能在GPCR激动剂（至少是α-肾上腺素能受体激动剂）诱导的心肌肥厚中起关键作用。
Cardiac hypertrophy is triggered in response to mechanical stress and various neurohumoral factors, such as G-protein coupling receptor (GPCR) and gp130 cytokine receptor agonists. Recent studies have suggested cardiac Z-disc plays a pivotal role to regulate these cellular responses. Here, we demonstrate stimulations with GPCR agonists (norepinephrine, angiotensin II, and endothelin 1) and phorbol ester activated and translocated protein kinase D1 (PKD1) to the Z-discs in neonatal rat cardiomyocytes in a protein kinase C (PKC)-dependent manner, whereas gp130 agonist did not. Especially, upon the α-adrenergic receptor agonist stimulations, following the PKCε–PKD1 complex formation, PKCε-dependent activation of PKD1 was essential to induce hypertrophic responses. Constitutively active mutant of either PKD1 or PKCε also induced cardiac hypertrophy ex vivo. Taken together, the PKCε–PKD1 complex at Z-discs could play a pivotal role in the cardiac hypertrophy induced by GPCR agonists, at least α-adrenergic receptor agonist.