Isensee, Joerg ORCID: 0000-0002-3390-0051, Diskar, Mandy, Waldherr, Steffen ORCID: 0000-0002-0936-579X, Buschow, Rene ORCID: 0000-0002-9800-2578, Hasenauer, Jan ORCID: 0000-0002-4935-3312, Prinz, Anke, Allgoewer, Frank, Herberg, Friedrich W. and Hucho, Tim ORCID: 0000-0002-4147-9308 (2014). Pain modulators regulate the dynamics of PKA-RII phosphorylation in subgroups of sensory neurons. J. Cell Sci., 127 (1). S. 216 - 230. CAMBRIDGE: COMPANY OF BIOLOGISTS LTD. ISSN 1477-9137
Full text not available from this repository.Abstract
Knowledge about the molecular structure of protein kinase A (PKA) isoforms is substantial. In contrast, the dynamics of PKA isoform activity in living primary cells has not been investigated in detail. Using a high content screening microscopy approach, we identified the RII beta subunit of PKA-II to be predominantly expressed in a subgroup of sensory neurons. The RII beta-positive subgroup included most neurons expressing nociceptive markers (TRPV1, NaV1.8, CGRP, IB4) and responded to pain-eliciting capsaicin with calcium influx. Isoform-specific PKA reporters showed in sensory-neuron-derived F11 cells that the inflammatory mediator PGE(2) specifically activated PKA-II but not PKA-I. Accordingly, pain-sensitizing inflammatory mediators and activators of PKA increased the phosphorylation of RII subunits (pRII) in subgroups of primary sensory neurons. Detailed analyses revealed basal pRII to be regulated by the phosphatase PP2A. Increase of pRII was followed by phosphorylation of CREB in a PKA-dependent manner. Thus, we propose RII phosphorylation to represent an isoform-specific readout for endogenous PKA-II activity in vivo, suggest RII beta as a novel nociceptive subgroup marker, and extend the current model of PKA-II activation by introducing a PP2A-dependent basal state.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-451501 | ||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1242/jcs.136580 | ||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | J. Cell Sci. | ||||||||||||||||||||||||||||||||||||||||
Volume: | 127 | ||||||||||||||||||||||||||||||||||||||||
Number: | 1 | ||||||||||||||||||||||||||||||||||||||||
Page Range: | S. 216 - 230 | ||||||||||||||||||||||||||||||||||||||||
Date: | 2014 | ||||||||||||||||||||||||||||||||||||||||
Publisher: | COMPANY OF BIOLOGISTS LTD | ||||||||||||||||||||||||||||||||||||||||
Place of Publication: | CAMBRIDGE | ||||||||||||||||||||||||||||||||||||||||
ISSN: | 1477-9137 | ||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/45150 |
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