Neuron. 2002 Aug 15;35(4):721-31.
cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation.
Bhave, G., Zhu, W., Wang, H., Brasier, D. J., Oxford, G. S., Gereau, R. W. 4th,
["Division of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA."]
["Division of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA."]
The capsaicin receptor, VR1 (also known as TRPV1), is a ligand-gated ion channel expressed on nociceptive sensory neurons that responds to noxious thermal and chemical stimuli. Capsaicin responses in sensory neurons exhibit robust potentiation by cAMP-dependent protein kinase (PKA). In this study, we demonstrate that PKA reduces VR1 desensitization and directly phosphorylates VR1. In vitro phosphorylation, phosphopeptide mapping, and protein sequencing of VR1 cytoplasmic domains delineate several candidate PKA phosphorylation sites. Electrophysiological analysis of phosphorylation site mutants clearly pinpoints Ser116 as the residue responsible for PKA-dependent modulation of VR1. Given the significant roles of VR1 and PKA in inflammatory pain hypersensitivity, VR1 phosphorylation at Ser116 by PKA may represent an important molecular mechanism involved in the regulation of VR1 function after tissue injury.
PMID: 12194871
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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Screening
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| Experimental screening | Non-experimental screening | Reference | ||||||||
| TRP channel construct | Interactor source | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
| TRPV1 |
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PKA | Inference | Prediction | 12194871 | |||||
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
|
Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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top
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| Functional consequence
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|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
| TRPV1 |
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PKA | In vitro PTM assay | Phosphorylation (Ser-116) | 12194871 | |||||||
| TRPV1 |
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PKA | Patch clamp | Activation | 12194871 | |||||||
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)