Oancea E, Meyer T
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cell. 1998 Oct 30;95(3):307-18. doi: 10.1016/s0092-8674(00)81763-8.
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 PKCgamma to the plasma membrane. While calcium acted rapidly, diacylglycerol binding to PKCgamma 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 PKCgamma responsive to persistent diacylglycerol increases combined with high- but not low-frequency calcium spikes.
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。在此，我们发现了一种分子机制，该机制确保传统蛋白激酶C（PKC）亚型被钙信号和二酰基甘油信号依次激活。触发重复性钙峰的受体刺激诱导了绿色荧光蛋白标记的PKCγ向质膜的平行重复易位。虽然钙作用迅速，但二酰基甘油与PKCγ的结合最初被一个假底物钳制所阻止，该假底物钳制使二酰基甘油结合位点无法接近，并延迟了钙和二酰基甘油介导的激酶激活。钙信号终止后，结合的二酰基甘油延长了激酶活性。这种分子解码机制的特性使PKCγ对持续的二酰基甘油增加以及高频而非低频钙峰产生反应。
