Epidermal growth factor receptor stimulation of diacylglycerol kinase.
Epidermal growth factor receptor stimulation of diacylglycerol kinase.
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表皮生长因子受体刺激二酰甘油激酶。
DOI：
10.1006/bbrc.1997.6237
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Stahl,WL
中科院分区：
文献类型：
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作者：
Montgomery,RB;Moscatello,DK;Wong,AJ;Stahl,WL
表皮生长因子受体（EGFR）激活磷脂信号信使磷脂酸（PA）在配体结合上的形成。我们探讨了慢性EGF刺激对表达完整EGFR和突变EGFR（EGFRvIII）的NIH3T3细胞中细胞PA的影响。EGFRvIII的存在使PA水平增加到慢性EGFR激活诱导的PA水平的两倍。脂肪酸甲酯分析显示含PA的油酸显著增加。磷脂酶D（PLD）的活性没有明显增加，检测和二酰基甘油（DAG）激酶试验表明，在激活的EGFR或EGFRvIII的存在下，二油酰DAG的显着偏好。PA水平低于DAG激酶激活预测的水平，这是由磷脂酸磷酸水解酶活性增加解释的。EGFR激酶和DAG激酶的特异性抑制剂通过EGFRvIII抑制DAG激酶活化和PA产生。通过长期暴露于配体或通过缺失突变激活EGFR激酶，刺激形成特定形式的信号传导PA。
The epidermal growth factor receptor (EGFR) activates formation of the phospholipid signal messenger phosphatidic acid (PA) on ligand binding. We explored the effects of chronic EGF stimulation on cellular PA in NIH3T3 cells expressing intact EGFR a mutant EGFR (EGFRvIII). The presence of EGFRvIII increased PA levels to twice those induced by chronic EGFR activation. Fatty acid methyl ester analysis revealed a marked increase in oleic acid containing PA. No apparent increase in phospholipase D (PLD) activity was detected, and diacylglycerol (DAG) kinase assays demonstrated a marked preference for dioleoyl DAG in the presence of activated EGFR or EGFRvIII. Levels of PA which were lower than would be predicted by DAG kinase activation are explained by increased phosphatidate phosphohydrolase activity. Specific inhibitors of EGFR kinase and DAG kinase suppressed DAG kinase activation and PA production by EGFRvIII. EGFR kinase activation by chronic exposure to ligand or by deletional mutation stimulates formation of a specific form of signalling PA.