A novel acylglycerol kinase that produces lysophosphatidic acid modulates cross talk with EGFR in prostate cancer cells.
A novel acylglycerol kinase that produces lysophosphatidic acid modulates cross talk with EGFR in prostate cancer cells.
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一种产生溶血磷脂酸的新型酰基甘油激酶可调节前列腺癌细胞中与 EGFR 的串扰。
DOI：
10.1083/jcb.200407123
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发表时间：
2005-06-06
期刊：
影响因子：
--
通讯作者：
Spiegel S
中科院分区：
文献类型：
--
作者：
Bektas M;Payne SG;Liu H;Goparaju S;Milstien S;Spiegel S
生物活性磷脂，溶血磷脂酸(LPA)和磷脂酸(PA)，调节与癌症发病相关的关键过程。在这里，我们报道了一种新的脂激酶的特征，命名为酰甘油激酶(AGK)，它分别磷酸化单酰甘油和二酰甘油形成LPA和PA。共聚焦显微镜和亚细胞分离表明AGK定位于线粒体。与同一患者的正常前列腺组织相比，前列腺癌组织中AGK的表达上调。前列腺癌PC-3细胞中AGK的表达明显增加LPA的形成和分泌。这种增加导致EGF受体的反式激活和细胞外信号相关激酶(ERK)1/2的持续激活，最终促进细胞增殖。AGK的表达也增加了迁移反应。相反，下调内源性AGK的表达可以抑制EGF而不是LPA诱导的ERK1/2的激活和通过细胞周期的S阶段的进展。因此，AGK可以放大EGF信号通路，可能在前列腺癌的病理生理过程中发挥重要作用。
The bioactive phospholipids, lysophosphatidic acid (LPA) and phosphatidic acid (PA), regulate pivotal processes related to the pathogenesis of cancer. Here, we report characterization of a novel lipid kinase, designated acylglycerol kinase (AGK), that phosphorylates monoacylglycerol and diacylglycerol to form LPA and PA, respectively. Confocal microscopy and subcellular fractionation suggest that AGK is localized to the mitochondria. AGK expression was up-regulated in prostate cancers compared with normal prostate tissues from the same patient. Expression of AGK in PC-3 prostate cancer cells markedly increased formation and secretion of LPA. This increase resulted in concomitant transactivation of the EGF receptor and sustained activation of extracellular signal related kinase (ERK) 1/2, culminating in enhanced cell proliferation. AGK expression also increased migratory responses. Conversely, down-regulating expression of endogenous AGK inhibited EGF- but not LPA-induced ERK1/2 activation and progression through the S phase of the cell cycle. Hence, AGK can amplify EGF signaling pathways and may play an important role in the pathophysiology of prostate cancer.
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鞘氨醇激酶表达会增加细胞内鞘氨醇1-磷酸盐，并促进细胞生长和存活。
DOI：
10.1083/jcb.147.3.545
发表时间：
1999-11-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Olivera A;Kohama T;Edsall L;Nava V;Cuvillier O;Poulton S;Spiegel S
通讯作者：
Spiegel S
影响因子：
56.9
作者：
Fang, YM;Vilella-Bach, M;Chen, J
通讯作者：
Chen, J
影响因子：
4.8
作者：
Hiroyama, R;Takenawa, T
通讯作者：
Takenawa, T
影响因子：
6.4
作者：
Kue, PF;Taub, JS;Daaka, Y
通讯作者：
Daaka, Y
影响因子：
8
作者：
Gschwind, A;Zwick, E;Ullrich, A
通讯作者：
Ullrich, A