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

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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
Creators:
CreatorsEmailORCIDORCID Put Code
Isensee, JoergUNSPECIFIEDorcid.org/0000-0002-3390-0051UNSPECIFIED
Diskar, MandyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waldherr, SteffenUNSPECIFIEDorcid.org/0000-0002-0936-579XUNSPECIFIED
Buschow, ReneUNSPECIFIEDorcid.org/0000-0002-9800-2578UNSPECIFIED
Hasenauer, JanUNSPECIFIEDorcid.org/0000-0002-4935-3312UNSPECIFIED
Prinz, AnkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Allgoewer, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herberg, Friedrich W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hucho, TimUNSPECIFIEDorcid.org/0000-0002-4147-9308UNSPECIFIED
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
Uncontrolled Keywords:
KeywordsLanguage
PROTEIN-KINASE-A; BOVINE CARDIAC-MUSCLE; ROOT GANGLION NEURONS; ENERGY-TRANSFER BRET; MUTANT MICE; THERMAL HYPERALGESIA; GENE-EXPRESSION; SUBUNIT; HOLOENZYME; REVEALSMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/45150

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