Cell
Volume 95, Issue 3, 30 October 1998, Pages 307-318
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Article
Protein Kinase C as a Molecular Machine for Decoding Calcium and Diacylglycerol Signals

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Abstract

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 PKCγ to the plasma membrane. While calcium acted rapidly, diacylglycerol binding to PKCγ 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 PKCγ responsive to persistent diacylglycerol increases combined with high- but not low-frequency calcium spikes.

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