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PMID:17194758
| Citation |
Pareek, TK, Keller, J, Kesavapany, S, Agarwal, N, Kuner, R, Pant, HC, Iadarola, MJ, Brady, RO and Kulkarni, AB (2007) Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. Proc. Natl. Acad. Sci. U.S.A. 104:660-5 |
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| 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. |
| Links |
PubMed PMC1752192 Online version:10.1073/pnas.0609916104 |
| Keywords |
Amino Acid Sequence; Animals; Base Sequence; Binding Sites; Calcium Signaling; Cyclin-Dependent Kinase 5/deficiency; Cyclin-Dependent Kinase 5/genetics; Cyclin-Dependent Kinase 5/metabolism; DNA Primers/genetics; Ganglia, Spinal/metabolism; Mice; Mice, Knockout; Models, Molecular; Molecular Sequence Data; Nociceptors/metabolism; Phosphorylation; Rats; Sequence Homology, Amino Acid; Signal Transduction; TRPV Cation Channels/chemistry; TRPV Cation Channels/genetics; TRPV Cation Channels/metabolism; Threonine/chemistry |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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