ArticleThe Journal of comparative neurology2009
Protein kinase D isoforms are expressed in rat and mouse primary sensory neurons and are activated by agonists of protease-activated receptor 2.
Article in The Journal of comparative neurology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Transcriptome of the human C2 dorsal root ganglia in C1-2 arthrodesis surgery: insight for neck pain.Brain : a journal of neurology · 2026Article
- Neurogenic differentiation 2 promotes inflammatory activation of macrophages in doxorubicin-induced myocarditis via regulating protein kinase D.BMC cardiovascular disorders · 2025Article
- Cluster Analysis of Short Sensory Profile Data Reveals Sensory-Based Subgroups in Autism Spectrum Disorder.International journal of molecular sciences · 2022Article
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- Legumain Induces Oral Cancer Pain by Biased Agonism of Protease-Activated Receptor-2.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Article
- Protein kinase D and Gβγ mediate sustained nociceptive signaling by biased agonists of protease-activated receptor-2.The Journal of biological chemistry · 2019Article
- Antagonism of the proinflammatory and pronociceptive actions of canonical and biased agonists of protease-activated receptor-2.British journal of pharmacology · 2016Article
- Protein Kinase D and Gβγ Subunits Mediate Agonist-evoked Translocation of Protease-activated Receptor-2 from the Golgi Apparatus to the Plasma Membrane.The Journal of biological chemistry · 2016Article
- Localization of TRPV1 and P2X3 in unmyelinated and myelinated vagal afferents in the rat.Journal of chemical neuroanatomy · 2016Article
- Hypersensitivity Induced by Activation of Spinal Cord PAR2 Receptors Is Partially Mediated by TRPV1 Receptors.PloS one · 2016Article
- Neutrophil Elastase Activates Protease-activated Receptor-2 (PAR2) and Transient Receptor Potential Vanilloid 4 (TRPV4) to Cause Inflammation and Pain.The Journal of biological chemistry · 2015Article
- Capsaicin-responsive corneal afferents do not contain TRPV1 at their central terminals in trigeminal nucleus caudalis in rats.Journal of chemical neuroanatomy · 2014Article
- Pathway-selective antagonism of proteinase activated receptor 2.British journal of pharmacology · 2014Article
- Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: evidence for a neurolymphocrine system.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Article
- In vitro cytotoxicity, pharmacokinetics, tissue distribution, and metabolism of small-molecule protein kinase D inhibitors, kb-NB142-70 and kb-NB165-09, in mice bearing human cancer xenografts.Cancer chemotherapy and pharmacology · 2013Article
- Role for substance p-based nociceptive signaling in progenitor cell activation and angiogenesis during ischemia in mice and in human subjects.Circulation · 2012Article
- Proteinase-activated receptors 1 and 2 regulate invasive behavior of human melanoma cells via activation of protein kinase D1.The Journal of investigative dermatology · 2012Article
- Depression of Ca(2+)/calmodulin-dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation.The Journal of comparative neurology · 2010Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Serine proteases generated during injury and inflammation cleave protease-activated receptor 2 (PAR(2)) on primary sensory neurons to induce neurogenic inflammation and hyperalgesia. Hyperalgesia requires sensitization of transient receptor potential vanilloid (TRPV) ion channels by mechanisms involving phospholipase C and protein kinase C (PKC). The protein kinase D (PKD) serine/threonine kinases are activated by diacylglycerol and PKCs and can phosphorylate TRPV1. Thus, PKDs may participate in novel signal transduction pathways triggered by serine proteases during inflammation and pain. However, it is not known whether PAR(2) activates PKD, and the expression of PKD isoforms by nociceptive neurons is poorly characterized. By using HEK293 cells transfected with PKDs, we found that PAR(2) stimulation promoted plasma membrane translocation and phosphorylation of PKD1, PKD2, and PKD3, indicating activation. This effect was partially dependent on PKCepsilon. By immunofluorescence and confocal microscopy, with antibodies against PKD1/PKD2 and PKD3 and neuronal markers, we found that PKDs were expressed in rat and mouse dorsal root ganglia (DRG) neurons, including nociceptive neurons that expressed TRPV1, PAR(2), and neuropeptides. PAR(2) agonist induced phosphorylation of PKD in cultured DRG neurons, indicating PKD activation. Intraplantar injection of PAR(2) agonist also caused phosphorylation of PKD in neurons of lumbar DRG, confirming activation in vivo. Thus, PKD1, PKD2, and PKD3 are expressed in primary sensory neurons that mediate neurogenic inflammation and pain transmission, and PAR(2) agonists activate PKDs in HEK293 cells and DRG neurons in culture and in intact animals. PKD may be a novel component of a signal transduction pathway for protease-induced activation of nociceptive neurons and an important new target for antiinflammatory and analgesic therapies.
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