TRESK (K2P18.1) Background Potassium Channel is Activated by Novel-Type Protein Kinase C via Dephosphorylation.

TRESK (K2P18.1) Background Potassium Channel is Activated by Novel-Type Protein Kinase C via Dephosphorylation. Mol Pharmacol. 2019 Apr 16;: Authors: Pergel E, Lengyel M, Enyedi P, Czirjak G Abstract TRESK (K2P18.1) background K+ channel is a major determinant of the excitability of primary sensory neurons. It has been reported that human TRESK is activated by the protein kinase C (PKC) activator PMA (phorbol 12-myristate 13-acetate) in Xenopus oocytes. In the present study, we investigated the mechanism of this PKC-dependent TRESK regulation. We show that TRESK is activated by the coexpression of the novel-type PKC isoforms eta and epsilon. The effect of PKC is not mediated by calcineurin phosphatase, which is known to evoke the calcium-dependent TRESK activation. The mutations of the calcineurin-binding sites in the channel (PQAAAS-AQAP) did not influence the PMA-induced increase of potassium current. In sharp contrast, the mutations of the target residue of calcineurin in TRESK, S264A and S264E, prevented the effect of PMA. The enforced phosphorylation of S264 by the coexpression of a microtubule-affinity regulating kinase construct (MARK2Δ) also abolished the PKC-dependent TRESK activation. These results suggest that in addition to calcineurin, PKC also regulates TRESK by changing the phosphorylation status of S264. The coexpression of PKC slowed down the recovery of the K+ current to the resting state after the calcineurin-depe...
Source: Molecular Medicine - Category: Molecular Biology Authors: Tags: Mol Pharmacol Source Type: research