Myristoylation alters retinoic acid-induced down-regulation of MARCKS in immortalized hippocampal cells.
Myristoylation alters retinoic acid-induced down-regulation of MARCKS in immortalized hippocampal cells.
复制标题
肉豆蔻酰化改变了视黄酸诱导的永生化海马细胞中 MARCKS 的下调。
DOI：
10.1006/bbrc.2000.3430
复制
发表时间：
2000
影响因子：
3.1
通讯作者：
Lenox,RH
中科院分区：
文献类型：
--
作者：
Wang,L;Watson,DG;Lenox,RH
肉豆蔻酰基化富丙氨酸C激酶底物（MARCKS）是大脑中重要的pkc底物，与大脑发育、细胞骨架重塑、钙/钙调素信号传导和神经可塑性有关。Macs基因序列编码一种具有三个高度保守结构域的蛋白质，包括一个5 '肉豆蔻酰化区域和一个25个氨基酸磷酸化位点结构域（PSD），它们参与将marks锚定在细胞膜上。在这项研究中，我们研究了肉豆蔻酰化信号在维甲酸（RA）治疗后转染大鼠海马细胞（H19-7）中调控MARCKS的作用。一个缺乏肉豆蔻酰化信号的突变体MARCKS通过在Macs基因2位用丙氨酸取代甘氨酸而被工程化，并被发现在转染细胞的细胞质部分中只表达。野生型转染marks的细胞暴露于RA后，marks明显从膜向胞质转移，而野生型marks的总蛋白没有明显变化。相反，转染突变体MARCKS的ra暴露细胞在细胞质和总蛋白组分中显示MARCKS蛋白的表达显著降低。这些数据表明，肉豆蔻酰基部分的缺失可能不仅改变了蛋白质在膜上的锚定，而且在RA反应中调节MARCKS蛋白的细胞水平方面发挥了新的作用。
The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent PKC-substrate in the brain, which has been implicated in brain development, cytoskeletal remodeling, calcium/calmodulin signaling, and neuroplasticity. The sequence of the Macs gene codes for a protein that has three highly conserved domains including a 5′ myristoylation region and a 25-amino-acid phosphorylation site domain (PSD), which are involved in anchoring MARCKS to the cellular membrane. In this study, we examined the role of the myristoylation signal in the regulation of MARCKS in transfected rat hippocampal cells (H19-7) following retinoic acid (RA) treatment. A mutant MARCKS lacking the myristoylation signal was engineered by substitution of alanine for glycine at position 2 of the Macs gene and was found to be exclusively expressed in the cytosol fraction of transfected cells. Exposure of the wild-type MARCKS-transfected cells to RA resulted in an apparent shift of MARCKS from the membrane to the cytosol, while the total protein of wild-type MARCKS was not significantly changed. In contrast, RA-exposed cells transfected with the mutant MARCKS revealed a dramatic reduction of expression of MARCKS protein in both cytosol and total protein fractions. These data suggest that the absence of the myristoyl moiety may not only alter the anchoring of the protein to the membrane but also play a novel role in modulating cellular levels of MARCKS protein in response to RA.