Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells.
Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells.
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DOI：
10.3390/ph3072045
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发表时间：
2010-07-02
期刊：
影响因子：
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通讯作者：
Meier KE
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文献类型：
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作者：
Chahal MS;Brauner DJ;Meier KE
磷脂酶D2（PLD 2）通过水解磷脂酰胆碱产生磷脂酸。PLD 2已被证明在增强肿瘤发生中起作用。表皮生长因子受体（EGFR）可以激活PLD 2并与PLD 2相互作用。缺乏内源性PLD 2的小鼠淋巴瘤EL 4细胞提出了一个独特的模型来阐明PLD 2在信号转导中的作用。在目前的研究中，我们研究了PLD 2对EGF反应的影响。Western印迹和RT-PCR用于确定亲本细胞和PLD 2转染子均表达内源性EGFR。与亲本细胞或表达无活性PLD 2的细胞相比，EGFR蛋白质的水平在表达活性PLD 2的细胞中增加。EGF刺激用活性PLD 2转染的EL 4细胞增殖，但不刺激亲本细胞或用失活PLD 2转染的细胞增殖。表达活性PLD 2的细胞中EGF介导的增殖依赖于EGFR和PI 3 K/Akt途径的活性，如使用蛋白激酶抑制剂的研究所证明的。与亲本细胞或表达无活性PLD 2的细胞相比，EGF诱导的通过合成细胞外基质的侵袭在表达活性PLD 2的细胞中增强。总之，数据表明PLD 2与EGFR协同作用以增强淋巴瘤细胞中的有丝分裂和侵袭。
Phospholipase D2 (PLD2) generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR) can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.