Regulation of diacylglycerol kinase α by phosphoinositide 3-kinase lipid products
Regulation of diacylglycerol kinase α by phosphoinositide 3-kinase lipid products
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DOI：
10.1074/jbc.m305635200
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发表时间：
2003-09-12
影响因子：
4.8
通讯作者：
Mérida, I
中科院分区：
文献类型：
--
作者：
Ciprés, A;Carrasco, S;Mérida, I
二酰基甘油激酶α (DAGKalpha)，像所有I型dagk一样，具有钙调节基序，作为酶活性和定位的负调节因子。因此，DAGKalpha被磷脂酶c偶联受体以钙依赖的方式激活。DAGKalpha在淋巴细胞中的第一个功能是调节白细胞介素2诱导的细胞周期进入。尽管如此，白细胞介素-2在没有胞质钙增加的情况下发挥其作用。我们研究了其他受体来源的信号来解释钙无关的DAGKalpha激活，并表明DAGKalpha在淋巴细胞中受到src样激酶依赖性磷酸肌肽3激酶（PI3K）激活的刺激。我们的研究结果表明，在体内，细胞中PI3K产物水平的增加足以诱导DAGKalpha活化，使DAGKalpha重新定位到完整的淋巴细胞质膜上。这种激活是同工异构体特异性的，因为其他I型dagk不受这种类型的调节。这些研究首次描述了在缺乏受体调节的钙增加的情况下，DAGKalpha激活和膜定位是PI3K激活的直接结果。
Diacylglycerol kinase alpha (DAGKalpha), like all type I DAGKs, has calcium regulatory motifs that act as negative regulators of enzyme activity and localization. Accordingly, DAGKalpha is activated by phospholipase C-coupled receptors in a calcium-dependent manner. One of the first functions attributed to DAGKalpha in lymphocytes was that of regulating interleukin 2-induced cell cycle entry. Interleukin-2 nonetheless exerts its action in the absence of cytosolic calcium increase. We have studied alternative receptor-derived signals to explain calcium-independent DAGKalpha activation, and show that DAGKalpha is stimulated by Src-like kinase-dependent phosphoinositide 3 kinase (PI3K) activation in lymphocytes. Our results demonstrate that, in vivo, the increase in cellular levels of PI3K products is sufficient to induce DAGKalpha activation, allowing DAGKalpha relocation to the intact lymphocyte plasma membrane. This activation is isoform-specific, because other type I DAGKs are not subject to this type of regulation. These studies are the first to describe a pathway in which, in the absence of receptorregulated calcium increase, DAGKalpha activation and membrane localization is a direct consequence of PI3K activation.