Diacylglycerol kinase δ regulates protein kinase C and epidermal growth factor receptor signaling
Diacylglycerol kinase δ regulates protein kinase C and epidermal growth factor receptor signaling
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DOI：
10.1073/pnas.0604104103
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发表时间：
2006-10-17
影响因子：
11.1
通讯作者：
Topham, Matthew K.
中科院分区：
文献类型：
--
作者：
Crotty, Tracy;Cai, Jinjin;Topham, Matthew K.
二酰基甘油激酶（DGKs）磷酸化二酰基甘油（DAG）以终止其信号传导。为了研究DGK δ，我们在小鼠中破坏了它的基因，发现DGK δ缺乏降低了EGF受体（EGFR）蛋白的表达和活性。与EGFR敲除小鼠类似，DGK δ缺失的幼鼠出生时眼睑张开，出生后不久死亡。PKCs被DAG激活并磷酸化EGFR以降低其表达和活性。在DGK δ敲除细胞中，我们发现DAG积累，EGFR苏氨酸磷酸化增加，其他PKC底物磷酸化增强，PKC自磷酸化增加，表明DGK δ通过调节PKC信号调节EGFR。
Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol (DAG) to terminate its signaling. To study DGK delta, we disrupted its gene in mice and found that DGK delta deficiency reduced EGF receptor (EGFR) protein expression and activity. Similar to EGFR knockout mice, DGK delta-deficient pups were born with open eyelids and died shortly after birth. PKCs are activated by DAG and phosphorylate EGFR to reduce its expression and activity. We found DAG accumulation, increased threonine phosphorylation of EGFR, enhanced phosphorylation of other PKC substrates, and increased PKC autophosphorylation in DGK delta knockout cells, indicating that DGK delta regulates EGFR by modulating PKC signaling.