Protein kinase C as a molecular machine for decoding calcium and diacylglycerol signals.
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.
Oancea
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Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Meyer
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T
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D020134:Catalytic Domain; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D004789:Enzyme Activation; D049452:Green Fluorescent Proteins; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008164:Luminescent Proteins; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D004075:Diglycerides; D007527:Isoenzymes; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D015240:Phorbol 12,13-Dibutyrate; C087857:protein kinase C gamma; D011493:Protein Kinase C; D002118:Calcium