Protein kinase C as a molecular machine for decoding calcium and diacylglycerol signals
Protein kinase C as a molecular machine for decoding calcium and diacylglycerol signals
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DOI：
10.1016/s0092-8674(00)81763-8
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发表时间：
1998-10-30
期刊：
影响因子：
64.5
通讯作者：
Meyer, T
中科院分区：
文献类型：
--
作者：
Oancea, E;Meyer, T
许多信号转导途径的特异性依赖于不同第二信使信号的时间协调。在这里，我们发现了一个分子机制，保证了传统的蛋白激酶C（PKC）亚型依次激活钙和甘油二酯信号。受体刺激，触发重复的钙峰诱导一个平行的重复易位的GFP标记的PKC γ的质膜。虽然钙迅速采取行动，二酰基甘油结合PKC γ最初阻止假底物钳，这使得二酰基甘油结合位点无法访问和延迟钙和二酰基甘油介导的激酶激活。终止后的钙信号，结合甘油二酯延长激酶活性。这种分子解码机器的特性使得PKC γ对持续的二酰基甘油增加以及高频率但非低频率的钙峰反应。
The specificity of many signal transduction pathways relies on the temporal coordination of different second messenger signals. Here we found a molecular mechanism which guarantees that conventional protein kinase C (PKC) isoforms are sequentially activated by calcium and diacylglycerol signals. Receptor stimuli that triggered repetitive calcium spikes induced a parallel repetitive translocation of GFP-tagged PKC gamma to the plasma membrane. While calcium acted rapidly, diacylglycerol binding to PKC gamma was initially prevented by a pseudosubstrate clamp, which kept the diacylglycerol-binding site inaccessible and delayed calcium- and diacylglycerol-mediated kinase activation. After termination of calcium signals, bound diacylglycerol prolonged kinase activity. The properties of this molecular decoding machine make PKC gamma responsive to persistent diacylglycerol increases combined with high- but not low-frequency calcium spikes.