Regulation of arachidonic acid release and cytosolic phospholipase A2 activation
Regulation of arachidonic acid release and cytosolic phospholipase A2 activation
复制标题
DOI：
10.1002/jlb.65.3.330
复制
发表时间：
1999-03-01
影响因子：
5.5
通讯作者：
Leslie, CC
中科院分区：
文献类型：
--
作者：
Gijón, MA;Leslie, CC
在许多细胞模型中，包括小鼠腹腔巨噬细胞，85-kDa胞质PLA（2）（cPLA（2））介导激动剂诱导的花生四烯酸释放。cPLA（2）受细胞内钙离子增加的调节，钙离子与氨基末端C2结构域结合并诱导其转运至核膜和内质网。丝裂原活化蛋白激酶（MAPK）对S505上cPLA（2）的磷酸化也有助于活化。在巨噬细胞中，酵母聚糖诱导细胞内钙离子短暂增加和MAPK活化，它们一起完全激活cPLA（2）并协同促进花生四烯酸释放。在巨噬细胞中存在调节cPLA（2）的替代途径，因为PMA和冈田酸诱导花生四烯酸释放而不增加钙。杆状病毒表达系统是研究cPLA（2）活化的有用模型。表达cPLA（2）的Sf 9细胞将花生四烯酸释放为A23187或冈田酸。cPLA（2）在Sf 9细胞中的多个位点上被磷酸化，并且S727的磷酸化优先被冈田酸诱导。然而，磷酸化位点是非必需的，并且在该模型中仅S505磷酸化部分地有助于cPLA（2）活化。尽管冈田酸不增加Sf 9细胞中的细胞内钙，但C2结构域的钙结合对于花生四烯酸的释放是必需的。A23187和冈田酸通过不同的机制激活cPLA（2），但都诱导Sf 9细胞中的核被膜易位。结果表明，替代调节途径可导致cPLA（2）激活和花生四烯酸释放。
The 85-kDa cytosolic PLA(2) (cPLA(2)) mediates agonist-induced arachidonic acid release in many cell models, including mouse peritoneal macrophages. cPLA(2) is regulated by an increase in intracellular calcium, which binds to an amino-terminal C2 domain and induces its translocation to the nuclear envelope and endoplasmic reticulum, Phosphorylation of cPLA(2) on S505 by mitogen-activated protein kinases (MAPK) also contributes to activation, In macrophages, zymosan induces a transient increase in intracellular calcium and activation of MAPK, which together fully activate cPLA(2) and synergistically promote arachidonic acid release, There are alternative pathways for regulating cPLA(2) in macrophages because PMA and okadaic acid induce arachidonic acid release without increasing calcium. The baculovirus expression system is a useful model to study cPLA(2) activation. Sf9 cells expressing cPLA(2) release arachidonic acid to either A23187 or okadaic acid. cPLA(2) is phosphorylated on multiple sites in Sf9 cells, and phosphorylation of S727 is preferentially induced by okadaic acid. However, the phosphorylation sites are non-essential and only S505 phosphorylation partially contributes to cPLA(2) activation in this model. Although okadaic acid does not increase intracellular calcium in Sf9 cells, calcium binding by the C2 domain is necessary for arachidonic acid release. A23187 and okadaic acid activate cPLA(2) by different mechanisms, yet both induce translocation to the nuclear envelope in Sf9 cells. The results demonstrate that alternative regulatory pathways can lead to cPLA(2) activation and arachidonic acid release.