Role of MARCKS in regulating endothelial cell proliferation.
Role of MARCKS in regulating endothelial cell proliferation.
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MARCKS 在调节内皮细胞增殖中的作用。
DOI：
10.1152/ajpcell.2000.279.5.c1611
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Davis,HW
中科院分区：
文献类型：
--
作者：
Zhao,Y;Neltner,BS;Davis,HW
豆蔻酰化富含丙氨酸的C激酶底物（MARCKS）是一种特异性的蛋白激酶C（PKC）底物，通过磷酸化修饰与丝状肌动蛋白（F-actin）和钙调蛋白（CaM）的结合，介导PKC信号转导。长期以来，PKC与细胞增殖有关，最近的研究表明MARCKS可能具有细胞生长抑制剂的功能。因此，在本研究中，我们研究了MARCKS蛋白的表达，分布和磷酸化在汇合前和汇合牛肺微血管内皮细胞（BPMEC）的存在或不存在的血管内皮生长因子（VEGF）。此外，我们通过研究MARCKS与F-肌动蛋白和钙调蛋白依赖性肌球蛋白轻链（MLC）磷酸化的关系，研究了MARCKS在这些细胞中的功能改变。我们的研究结果表明，MARCKS蛋白在BPMEC增殖过程中下调。减少MARCKS与F-肌动蛋白的关联，增加肌动蛋白聚合和钙调蛋白依赖的MLC磷酸化似乎介导BPMEC生长过程中细胞的形状变化和运动性。与此相反，VEGF刺激MARCKS磷酸化而不改变蛋白表达在BPMEC增殖，这可能会导致减少MARCKS和肌动蛋白或CaM之间的相互作用，导致肌动蛋白重组和MLC磷酸化。我们的数据表明MARCKS在内皮细胞增殖过程中的调节作用。
Myristoylated alanine-rich C kinase substrate (MARCKS), as a specific protein kinase C (PKC) substrate, mediates PKC signaling through its phosphorylation and subsequent modification of its association with filamentous actin (F-actin) and calmodulin (CaM). PKC has long been implicated in cell proliferation, and recent studies have suggested that MARCKS may function as a cell growth suppressor. Therefore, in the present study, we investigated MARCKS protein expression, distribution, and phosphorylation in preconfluent and confluent bovine pulmonary microvascular endothelial cells (BPMEC) in the presence or absence of the vascular endothelial growth factor (VEGF). In addition, we examined functional alterations of MARCKS in these cells by studying the association of MARCKS with F-actin and CaM-dependent myosin light chain (MLC) phosphorylation. Our results indicate that MARCKS protein is downregulated during BPMEC proliferation. Decreased MARCKS association with F-actin, increased actin polymerization, and CaM-dependent MLC phosphorylation appear to mediate cell shape changes and motility during BPMEC growth. In contrast, VEGF stimulated MARCKS phosphorylation without alteration of protein expression during BPMEC proliferation, which may result in reduced interaction between MARCKS and actin or CaM, leading to actin reorganization and MLC phosphorylation. Our data suggest a regulatory role of MARCKS during endothelial cell proliferation.