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PKCα: a versatile key for decoding the cellular calcium toolkit

G. Reither,M. Schaefer,P. Lipp

Published 2006 in Journal of Cell Biology

ABSTRACT

Conventional protein kinases C (cPKCs) play an essential role in signal transduction and are believed to integrate both global Ca2+ transients and diacylglycerol signals. We provide evidence that PKCα is a ubiquitous readout sensor for the cellular Ca2+ toolkit, including highly restricted elementary Ca2+ release. Threshold stimulations of cells with Ca2+-mobilizing agonists resulted in PKCα translocation events with limited spatial spreads (<4 μm) comprising two groups of lifetimes; brief events (400–1,500 ms) exclusively mediated by Ca2+–C2 domain membrane interactions and long-lasting events (>4 s) resulting from longer DAG-C1a domain–mediated membrane interactions. Although upon uncaging NP-EGTA, which is a caged Ca2+ compound, WT-PKCα displayed rapid membrane translocations within <250 ms, PKCα constructs with C2 domains mutated in their Ca2+-binding region lacked any Ca2+-dependent translocation. Flash photolysis of diazo-2, a photosensitive caged Ca2+ buffer, revealed a biphasic membrane dissociation (slow and fast period) of WT-PKCα. The slow phase was absent in cells expressing PKCα-constructs containing mutated C1a-domains with largely reduced DAG binding. Thus, two groups of PKCα membrane interactions coexist; C2- and C1a-mediated interactions with different lifetimes but rapid interconversion. We conclude that PKCα can readout very fast and, spatially and temporally, very complex cellular Ca2+ signals. Therefore, cPKCs are important transducers for the ubiquitous cellular Ca2+ signaling toolkit.

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