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PKCα: a versatile key for decoding the cellular calcium toolkit
Conventional protein kinases C (cPKCs) play an essential role in signal transduction and are believed to integrate both global Ca(2+) transients and diacylglycerol signals. We provide evidence that PKCα is a ubiquitous readout sensor for the cellular Ca(2+) toolkit, including highly restricted eleme...
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064258/ https://www.ncbi.nlm.nih.gov/pubmed/16893971 http://dx.doi.org/10.1083/jcb.200604033 |
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author | Reither, Gregor Schaefer, Michael Lipp, Peter |
author_facet | Reither, Gregor Schaefer, Michael Lipp, Peter |
author_sort | Reither, Gregor |
collection | PubMed |
description | Conventional protein kinases C (cPKCs) play an essential role in signal transduction and are believed to integrate both global Ca(2+) transients and diacylglycerol signals. We provide evidence that PKCα is a ubiquitous readout sensor for the cellular Ca(2+) toolkit, including highly restricted elementary Ca(2+) release. Threshold stimulations of cells with Ca(2+)-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 Ca(2+)–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 Ca(2+) compound, WT-PKCα displayed rapid membrane translocations within <250 ms, PKCα constructs with C2 domains mutated in their Ca(2+)-binding region lacked any Ca(2+)-dependent translocation. Flash photolysis of diazo-2, a photosensitive caged Ca(2+) 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 Ca(2+) signals. Therefore, cPKCs are important transducers for the ubiquitous cellular Ca(2+) signaling toolkit. |
format | Text |
id | pubmed-2064258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20642582007-11-29 PKCα: a versatile key for decoding the cellular calcium toolkit Reither, Gregor Schaefer, Michael Lipp, Peter J Cell Biol Research Articles Conventional protein kinases C (cPKCs) play an essential role in signal transduction and are believed to integrate both global Ca(2+) transients and diacylglycerol signals. We provide evidence that PKCα is a ubiquitous readout sensor for the cellular Ca(2+) toolkit, including highly restricted elementary Ca(2+) release. Threshold stimulations of cells with Ca(2+)-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 Ca(2+)–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 Ca(2+) compound, WT-PKCα displayed rapid membrane translocations within <250 ms, PKCα constructs with C2 domains mutated in their Ca(2+)-binding region lacked any Ca(2+)-dependent translocation. Flash photolysis of diazo-2, a photosensitive caged Ca(2+) 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 Ca(2+) signals. Therefore, cPKCs are important transducers for the ubiquitous cellular Ca(2+) signaling toolkit. The Rockefeller University Press 2006-08-14 /pmc/articles/PMC2064258/ /pubmed/16893971 http://dx.doi.org/10.1083/jcb.200604033 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Reither, Gregor Schaefer, Michael Lipp, Peter PKCα: a versatile key for decoding the cellular calcium toolkit |
title | PKCα: a versatile key for decoding the cellular calcium toolkit |
title_full | PKCα: a versatile key for decoding the cellular calcium toolkit |
title_fullStr | PKCα: a versatile key for decoding the cellular calcium toolkit |
title_full_unstemmed | PKCα: a versatile key for decoding the cellular calcium toolkit |
title_short | PKCα: a versatile key for decoding the cellular calcium toolkit |
title_sort | pkcα: a versatile key for decoding the cellular calcium toolkit |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064258/ https://www.ncbi.nlm.nih.gov/pubmed/16893971 http://dx.doi.org/10.1083/jcb.200604033 |
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