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Isensee, J.* ; Diskar, M.* ; Waldherr, S.* ; Buschow, R.* ; Hasenauer, J. ; Prinz, A.* ; Allgöwer, F.* ; Herberg, F.W.* ; Hucho, T.*

Pain modulators regulate the dynamics of PKA-RII phosphorylation in subgroups of sensory neurons.

J. Cell Sci. 127, 216-229 (2014)
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Knowledge about the molecular structure of 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 RIIβ subunit of PKA-II to be predominantly expressed in a subgroup of sensory neurons. The RIIβ-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 PGE2 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 RIIβ as a novel nociceptive subgroup marker, and extend the current model of PKA-II activation by introducing a PP2A-dependent basal state.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Protein Kinase A ; Rii Phosphorylation ; Camp Response Element-binding Protein ; Nociception ; Sensitization; Protein-kinase-a; Bovine Cardiac-muscle; Root Ganglion Neurons; Energy-transfer Bret; Mutant Mice; Thermal Hyperalgesia; Gene-expression; Subunit; Holoenzyme; Reveals
ISSN (print) / ISBN 0021-9533
e-ISSN 1477-9137
Quellenangaben Volume: 127, Issue: 1, Pages: 216-229 Article Number: , Supplement: ,
Publisher Company of Biologists
Publishing Place Cambridge
Reviewing status Peer reviewed