Phosphorylation of Vanilloid Receptor 1 by Ca 2+/Calmodulin-dependent Kinase II Regulates Its Vanilloid Binding

Jooyoung Jung, Jae Soo Shin, Soon Youl Lee, Sun Wook Hwang, Jaeyeon Koo, Hawon Cho, Uhtaek Oh

Research output: Contribution to journalArticlepeer-review

234 Citations (Scopus)


Vanilloid receptor 1 (VR1), a capsaicin receptor, is known to play a major role in mediating inflammatory thermal nociception. Although the physiological role and biophysical properties of VR1 are known, the mechanism of its activation by ligands is poorly understood. Here we show that VR1 must be phosphorylated by Ca2+-calmodulin dependent kinase II (CaMKII) before its activation by capsaicin. In contrast, the dephosphorylation of VR1 by calcineurin leads to a desensitization of the receptor. Moreover, point mutations in VR1 at two putative consensus sites for CaMKII failed to elicit capsaicin-sensitive currents and caused a concomitant reduction in VR1 phosphorylation in vivo. Such mutants also lost their high affinity binding with [3H]resiniferatoxin, a potent capsaicin receptor agonist. We conclude that the dynamic balance between the phosphorylation and dephosphorylation of the VR1 channel by CaMKII and calcineurin, respectively, controls the activation/ desensitization states by regulating VR1 binding. Furthermore, because sensitization by protein kinase A and C converge at these sites, phosphorylation stress in the cell appears to control a wide range of excitabilities in response to various adverse stimuli.

Original languageEnglish
Pages (from-to)7048-7054
Number of pages7
JournalJournal of Biological Chemistry
Issue number8
Publication statusPublished - 2004 Feb 20
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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