CYTOSOLIC PHOSPHOLIPASE-A2 IS COUPLED TO HORMONALLY REGULATED RELEASE OF ARACHIDONIC-ACID
CYTOSOLIC PHOSPHOLIPASE-A2 IS COUPLED TO HORMONALLY REGULATED RELEASE OF ARACHIDONIC-ACID
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DOI：
10.1073/pnas.89.13.6147
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发表时间：
1992-07-01
影响因子：
11.1
通讯作者：
KNOPF, JL
中科院分区：
文献类型：
--
作者：
LIN, LL;LIN, AY;KNOPF, JL
胞质磷脂酶A2（cPLA 2）以Ca 2+依赖的方式结合天然膜囊泡，导致花生四烯酸的选择性释放，从而暗示cPLA 2在神经调节的类花生酸生产中。在这里，我们报告说，中国仓鼠卵巢（CHO）细胞过度表达cPLA 2与ATP或凝血酶的治疗导致花生四烯酸的释放增加相比，父母CHO细胞，证明cPLA 2的激素偶联。相反，CHO细胞过表达哺乳动物PLA 2（sPLA 2-II）的分泌形式未能显示任何增加的激素反应。有趣的是，我们已经注意到，用各种各样的试剂激活cPLA 2会刺激cPLA 2在丝氨酸残基上的磷酸化。用星形孢菌素预处理细胞阻断ATP介导的cPLA 2磷酸化，并强烈抑制该酶的活化。在ATP处理的细胞制备的裂解物中也观察到cPLA 2活性增加，并且对磷酸酶处理敏感。这些结果表明，除了Ca ~（2+），cPLA 2的磷酸化在激动剂诱导的cPLA 2活化中起重要作用。
Cytosolic phospholipase A2 (cPLA2) binds to natural membrane vesicles in a Ca2+-dependent fashion, resulting in the selective release of arachidonic acid, thus implicating cPLA2 in the hormonally regulated production of eicosanoids. Here we report that the treatment of Chinese hamster ovary (CHO) cells overexpressing cPLA2 with ATP or thrombin resulted in an increased release of arachidonic acid as compared with parental CHO cells, demonstrating the hormonal coupling of cPLA2. In contrast, CHO cells overexpressing a secreted form of mammalian PLA2 (sPLA2-II) failed to show any increased hormonal responsiveness. Interestingly, we have noted that the activation of cPLA2 with a wide variety of agents stimulates the phosphorylation of cPLA2 on serine residues. Pretreatment of cells with staurosporin blocked the ATP-mediated phosphorylation of cPLA2 and strongly inhibited the activation of the enzyme. Increased cPLA2 activity was also observed in lysates prepared from ATP-treated cells and was sensitive to phosphatase treatment. These results suggest that in addition to Ca2+, the phosphorylation of cPLA2 plays an important role in the agonist-induced activation of cPLA2.