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首页> 外文期刊>American Journal of Physiology >PKC-induced ERK1/2 interactions and downstream effectors in ovine cerebral arteries.
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PKC-induced ERK1/2 interactions and downstream effectors in ovine cerebral arteries.

机译：PKC诱导的ERK1 / 2相互作用和绵羊脑动脉下游效应子。

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Both protein kinase C (PKC) and extracellular signal-regulated kinases (ERK1/2) are involved in mediating vascular smooth muscle contraction. We tested the hypotheses that in addition to PKC activation of ERK1/2, by negative feedback ERKs modulate PKC-induced contraction, and that their interactions modulate both thick and thin myofilament pathways. In ovine middle cerebral arteries (MCA), we measured isometric tension and intracellular free calcium concentration ([Ca(2+)](i)) responses to PKC stimulation [phorbol 12,13-dibutyrate (PDBu), 3 x 10(-6) M] in the absence or presence of ERK1/2 inhibition (U-0126, 10(-5) M). After PDBu +/- ERK1/2 inhibition, we also examined by Western immunoblot the levels of total and phosphorylated ERK1/2, caldesmon(Ser789), myosin light chain(20) (MLC(20)), and CPI-17. PDBu induced significant increase in tension in the absence of increased [Ca(2+)](i). PDBu also increased phosphorylated ERK1/2 levels, a response blocked by U-0126. In turn, U-0126 augmented PDBu-induced contractions. PDBu also was associated with significant increases in phosphorylated caldesmon(Ser789) and MLC(20) levels, each of which peaked at 5 to 10 min. PDBu also increased phosphorylated CPI-17 levels, which peaked at 2 to 3 min. Rho kinase inhibition (Y-27632, 3 x 10(-7) M) did not alter PDBu-induced contraction. These results support the idea that PKC activation can increase CPI-17 phosphorylation to decrease myosin light chain phosphatase activity. In turn, this increases MLC(20) phosphorylation in the thick filament pathway and increases Ca(2+) sensitivity. In addition, ERK1/2-dependent phosphorylation of caldesmon(Ser789) was not necessary for PDBu-induced contraction and appears not to be involved in the reversal of caldesmon's inhibitory effect on actin-myosin ATPase.
机译：蛋白激酶C（PKC）和细胞外信号调节激酶（ERK1 / 2）均参与介导血管平滑肌收缩。我们测试了这样的假设：除PKC激活ERK1 / 2外，通过负反馈ERK调节PKC诱导的收缩，并且它们的相互作用调节厚和薄的肌丝通路。在绵羊中脑动脉（MCA），我们测量了等轴测张力和细胞内游离钙浓度（[Ca（2 +）]（i））对PKC刺激的反应[佛波醇12,13-二丁酸酯（PDBu），3 x 10（- 6）M]不存在或存在ERK1 / 2抑制作用（U-0126，10（-5）M）。 PDBu +/- ERK1 / 2抑制后，我们还通过Western免疫印迹检查了总ERK1 / 2和磷酸化ERK1 / 2，caldesmon（Ser789），肌球蛋白轻链（20）（MLC（20））和CPI-17的水平。在不增加[Ca（2 +）]（i）的情况下，PDBu导致张力显着增加。 PDBu还增加了磷酸化ERK1 / 2的水平，这一反应被U-0126阻止。反过来，U-0126增加了PDBu引起的收缩。 PDBu还与磷酸化的caldesmon（Ser789）和MLC（20）水平显着增加有关，它们各自在5至10分钟达到峰值。 PDBu还增加了磷酸化CPI-17的水平，该水平在2-3分钟达到峰值。 Rho激酶抑制（Y-27632，3 x 10（-7）M）不会改变PDBu诱导的收缩。这些结果支持了PKC激活可以增加CPI-17磷酸化以降低肌球蛋白轻链磷酸酶活性的想法。反过来，这会增加粗丝路径中的MLC（20）磷酸化并增加Ca（2+）敏感性。此外，PDK诱导的收缩不一定需要ERK1 / 2依赖性的caldesmon（Ser789）磷酸化，并且似乎不参与caldesmon对肌动蛋白-肌球蛋白ATPase的抑制作用的逆转。

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