Ca2+-controlled competitive diacylglycerol binding of protein kinase C isoenzymes in living cells
- PMID: 12391024
- PMCID: PMC2173038
- DOI: 10.1083/jcb.200203048
Ca2+-controlled competitive diacylglycerol binding of protein kinase C isoenzymes in living cells
Abstract
The cellular decoding of receptor-induced signaling is based in part on the spatiotemporal activation pattern of PKC isoforms. Because classical and novel PKC isoforms contain diacylglycerol (DAG)-binding C1 domains, they may compete for DAG binding. We reasoned that a Ca2+-induced membrane association of classical PKCs may accelerate the DAG binding and thereby prevent translocation of novel PKCs. Simultaneous imaging of fluorescent PKC fusion proteins revealed that during receptor stimulation, PKC alpha accumulated in the plasma membrane with a diffusion-limited kinetic, whereas translocation of PKC epsilon was delayed and attenuated. In BAPTA-loaded cells, however, a selective translocation of PKC epsilon, but not of coexpressed PKC alpha, was evident. A membrane-permeable DAG analogue displayed a higher binding affinity for PKC epsilon than for PKC alpha. Subsequent photolysis of caged Ca2+ immediately recruited PKC alpha to the membrane, and DAG-bound PKC epsilon was displaced. At low expression levels of PKC epsilon, PKC alpha concentration dependently prevented the PKC epsilon translocation with half-maximal effects at equimolar coexpression. Furthermore, translocation of endogenous PKCs in vascular smooth muscle cells corroborated the model that a competition between PKC isoforms for DAG binding occurs at native expression levels. We conclude that Ca2+-controlled competitive DAG binding contributes to the selective recruitment of PKC isoforms after receptor activation.
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