Cyclin-dependent Kinase 5 Modulates Nociceptive Signaling Through Direct Phosphorylation of Transient Receptor Potential Vanilloid 1.
From: Functional Genomics Section, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Jan 2007
- ISSN: 0027-8424
- Volume: 104
- Issue: 2
- Pages: 660-5
- Medium: Print
- Language: English
- Citation (JAMA): Pareek Tej K, Keller Jason, Kesavapany Sashi, et al. Cyclin-dependent Kinase 5 Modulates Nociceptive Signaling Through Direct Phosphorylation of Transient Receptor Potential Vanilloid 1.. Proc. Natl. Acad. Sci. U.S.A. Jan 2007;104:660-5
Abstract
Transient receptor potential vanilloid 1 (TRPV1), a ligand-gated cation channel highly expressed in small-diameter sensory neurons, is activated by heat, protons, and capsaicin. The phosphorylation of TRPV1 provides a versatile regulation of intracellular calcium levels and is critical for TRPV1 function in responding to a pain stimulus. We have previously reported that cyclin-dependent kinase 5 (Cdk5) activity regulates nociceptive signaling. In this article we report that the Cdk5-mediated phosphorylation of TRPV1 at threonine-407 can modulate agonist-induced calcium influx. Inhibition of Cdk5 activity in cultured dorsal root ganglia neurons resulted in a significant reduction of TRPV1-mediated calcium influx, and this effect could be reversed by restoring Cdk5 activity. Primary nociceptor-specific Cdk5 conditional-knockout mice showed reduced TRPV1 phosphorylation, resulting in significant hypoalgesia. Thus, the present study indicates that Cdk5-mediated TRPV1 phosphorylation is important in the regulation of pain signaling.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Calcium Signaling, Cyclin-Dependent Kinase 5, DNA Primers, Ganglia, Spinal, Mice, Mice, Knockout, Models, Molecular, Molecular Sequence Data, Nociceptors, Phosphorylation, Rats, Sequence Homology, Amino Acid, Signal Transduction, TRPV Cation Channels, Threonine
Check for Full Text / PubMed Unique Identifier (PMID): 17194758
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