Myosin phosphatase isoform switching in vascular smooth muscle development
Myosin phosphatase isoform switching in vascular smooth muscle development
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DOI：
10.1016/j.yjmcc.2005.07.009
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发表时间：
2006-02-01
影响因子：
5
通讯作者：
Fisher, SA
中科院分区：
文献类型：
--
作者：
Payne, MC;Zhang, HY;Fisher, SA
我们正在使用肌球蛋白磷酸酶靶向亚基 (MYPT1)，它是研究平滑肌表型多样性的模型基因。肌球蛋白磷酸酶 (MP) 是平滑肌松弛的主要效应器，而 MYPT1 是调节平滑肌张力的信号的关键靶标。在门静脉高压模型中，我们之前显示了门静脉和上游肠系膜动脉中 MYPTI 亚型表达的动态变化。我们假设这代表了肌肉肥大胎儿表型特征的逆转。在这里，我们研究了血管平滑肌表型规范期间的 NIP。出生后第 6 天和第 12 天之间，门静脉中 MYPTI 的表达增加了大约两倍，MP 活性也有类似的增加。 MYPT1 从 C 端亮氨酸拉链 (LZ) 阳性剪接变体亚型转变为 LZ 阴性剪接变体亚型。这与对cGMP介导的血管舒张从敏感(10(-7)M)到抵抗的转变是一致的。这与 MYPTI C 端 LZ 是 MP 的 cGMP 依赖性激活所必需的模型一致。其他收缩蛋白表达的一致变化与从慢速收缩表型到快相收缩表型的转变一致。相比之下，主动脉平滑肌在整个发育过程中表达 MYPTI LZ 阳性同工型，并对 cGMP 松弛。我们认为，新生儿血管平滑肌表型规范过程中的 MP 异构体转换可能决定从胎儿循环到成人循环过渡过程中血管对 NO/cGMP 信号传导的反应变化。 (c) 2005 Elsevier Ltd. 保留所有权利。
We are using the myosin phosphatase targeting Subunit (MYPT1) its a model gene to study smooth muscle phenotypic diversity. Myosin phosphatase (MP) is the primary effector of smooth muscle relaxation, and MYPT1 is a key target of signals that regulate smooth muscle tone. In a model of portal hypertension we previously showed dynamic changes in the expression of MYPTI isoforms in the portal vein and upstream mesenteric artery. We hypothesized that this represents a reversion to the fetal phenotype characteristic of muscle hypertrophy. Here we Studied NIP during vascular smooth muscle phenotypic specification. Between postnatal days 6 and 12 the expression of MYPTI increased approximately twofold in portal vein with a similar increase in MP activity. MYPT1 switched from C-terminal leucine zipper (LZ) positive to LZ negative splice variant isoforms. This was concordant with a switch from sensitive (10(-7) M) to resistant to cGMP-mediated vascular relaxation. This is consistent with the model in which the MYPTI C-terminal LZ is required for cGMP-dependent activation of MP. Concordant changes in the expression of other contractile proteins were consistent with a switch from a slow-tonic to a fast-phasic contractile phenotype. In contrast aortic smooth muscle throughout development expressed the MYPTI LZ positive isoform and relaxed to cGMP. We propose that MP isoform switching during neonatal vascular smooth muscle phenotypic specification may determine changing vascular responses to NO/cGMP signaling in the transition from the fetal to the adult circulation. (c) 2005 Elsevier Ltd. All rights reserved.