| First Author | Zhao X | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 1 | Pages | 108191 |
| PubMed ID | 33027667 | Mgi Jnum | J:300253 |
| Mgi Id | MGI:6489022 | Doi | 10.1016/j.celrep.2020.108191 |
| Citation | Zhao X, et al. (2020) PKCepsilon SUMOylation Is Required for Mediating the Nociceptive Signaling of Inflammatory Pain. Cell Rep 33(1):108191 |
| abstractText | Despite the important roles of protein kinase Cepsilon (PKCepsilon) and transient receptor potential vanilloind 1 (TRPV1) in inflammatory hypersensitivity, how PKCepsilon is involved in the regulation of thermal hyperalgesia is not fully understood. We report here that PKCepsilon is SUMOylated at a C-terminal lysine residue (K534), which enhances the sensitivity of the TRPV1 channel. We demonstrate that PKCepsilon phosphorylation promotes its SUMOylation, which in turn regulates the phosphorylation level of TRPV1 serine 800 residue via controlling the binding of PKCepsilon and TRPV1 and increased PKCepsilon kinase activity. More importantly, the reduced ability of PKCepsilon knockdown mice to develop inflammatory thermal hyperalgesia was rescued by viral infection of lumbar 4/5 dorsal root ganglia neurons of wild-type PKCepsilon, but not the SUMOylation-deficient PKCepsilon mutant. Therefore, the SUMOylation of PKCepsilon potentiates inflammatory thermal hyperalgesia through stabilizing the interaction with TRPV1 to enhance its function by phosphorylation. |
