INDRA statements for KCNK18

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Statements

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phosphosite cbn pc11 biopax bel_lc signor biogrid lincs_drug tas hprd trrust ctd virhostnet phosphoelm drugbank omnipath | geneways tees isi trips rlimsp medscan sparser eidos reach
reading
KCNK18 affects Tubulin
| 18 10
KCNK18 binds Tubulin.
| 18 9
Tubulin binds KCNK18. 25 / 25
| 17 8
sparser
"These observations indicate that the binding of tubulin to TRESK loop does not depend on a single short determinant in the sequence, but there are multiple (at least two) contact points between the two proteins."
24830385
reach
"The above pharmacological and overexpression experiments did not shed light on the functional relevance of the interaction between TRESK and tubulin."
24830385
reach
"These observations indicate that the binding of tubulin to TRESK loop does not depend on a single short determinant in the sequence, but there are multiple (at least two) contact points between the two proteins."
24830385
reach
"We provided evidence suggesting that the PKA dependent docking of 14-3-3 interfered with the binding of tubulin to TRESK."
24830385
sparser
"In order to further verify and also statistically evaluate the binding of tubulin to the cytoplasmic loop of TRESK, we performed four pairs of independent pull-down assays from mouse brain cytosol with either the bait protein (fragment 174–280) or only the control resin."
24830385
sparser
"The architectural complexity level of tubulin (e.g. monomer, dimer, oligomer, protofilament, microtubule) interacting with TRESK also has not yet been defined."
24830385
sparser
"We provided evidence suggesting that the PKA-dependent docking of 14-3-3 interfered with the binding of tubulin to TRESK."
24830385
sparser
"Although tubulin binds to TRESK in vitro , it remains to be established whether the two proteins also interact in the living cell."
24830385
sparser
"The most plausible explanation of this result is that the functional unit of tubulin, the α–β heterodimer associates to TRESK."
24830385
sparser
"Therefore, we initially tested the binding of tubulin to TRESK loop, if this serine was or was not phosphorylated with protein kinase A before the usual pull-down assay."
24830385
sparser
"In addition to the known TRESK-interacting proteins (calcineurin and 14-3-3), we detected substantial binding of tubulin to the cytoplasmic loop of TRESK."
24830385
sparser
"The persistent binding of tubulin to TRESK loop during the long washing step and NaCl gradient encouraged us to also demonstrate the interaction in pull-down assays."
24830385
sparser
"Our results also hint at the possibility that the interaction between TRESK and tubulin is conditional."
24830385
reach
"Our results also hint at the possibility that the interaction between TRESK and tubulin is conditional."
24830385
sparser
"In the following experiments we examined the interaction between TRESK loop and tubulin in a different experimental context."
24830385
reach
"P2X2 channel and TRESK may bind tubulin with a similar mechanism."
24830385
sparser
"Therefore we concluded that fragment 256–271 is a major determinant of the interaction of tubulin with the cytoplasmic loop of TRESK."
24830385
reach
"The cytoplasmic loop of the distantly related Danio rerio (zebrafish) TRESK (amino acids 174-284) also binds tubulin (as a GST-fusion protein, XREF_FIG, compare lane 3 to lanes 1 and 2)."
24830385
reach
"Although tubulin binds to TRESK in vitro, it remains to be established whether the two proteins also interact in the living cell."
24830385
sparser
"Together with the mass spectrometry data of the corresponding band from affinity chromatography, we consider it as proof that the cytoplasmic loop of TRESK interacted with tubulin in the pull-down assays."
24830385
sparser
"In fact, the reduced interaction of TRESK loop with tubulin could have been caused by either the binding of 14-3-3 to the loop or the phosphorylation of the 14-3-3-binding site by PKA in this experiment."
24830385
sparser
"The above pharmacological and overexpression experiments did not shed light on the functional relevance of the interaction between TRESK and tubulin."
24830385
sparser
"P2X2 channel and TRESK may bind tubulin with a similar mechanism."
24830385
sparser
"The cytoplasmic loop of the distantly related Danio rerio (zebrafish) TRESK (amino acids 174–284) also binds tubulin (as a GST-fusion protein, xref , compare lane 3 to lanes 1 and 2 )."
24830385
reach
"The persistent binding of tubulin to TRESK loop during the long washing step and NaCl gradient encouraged us to also demonstrate the interaction in pull-down assays."
24830385
Tubulin binds KCNK18 and serine. 1 / 1
| 1
reach
"Therefore, we initially tested the binding of tubulin to TRESK loop, if this serine was or was not phosphorylated with protein kinase A before the usual pull-down assay."
24830385
PPP3 binds Tubulin and KCNK18. 1 / 1
| 1
sparser
"Human TRESK loop (174–280) interacted with tubulin and calcineurin (similarly to its murine counterpart), in contrast to glutathione agarose and the GST-only control ( xref , compare lane 3 to lanes 1 and 2 , tubulin is indicated with an asterisk )."
24830385
KCNK18 inhibits Tubulin.
| 1
KCNK18 inhibits Tubulin. 1 / 1
| 1
reach
"Phosphorylation of TRESK and the consequent anchoring of 14-3-3 may occlude the tubulin binding site of TRESK, and prevent the association of tubulin to the channel under resting conditions."
24830385
Tubulin affects KCNK18
| 18 9
Tubulin binds KCNK18. 25 / 25
| 17 8
sparser
"These observations indicate that the binding of tubulin to TRESK loop does not depend on a single short determinant in the sequence, but there are multiple (at least two) contact points between the two proteins."
24830385
reach
"The above pharmacological and overexpression experiments did not shed light on the functional relevance of the interaction between TRESK and tubulin."
24830385
reach
"These observations indicate that the binding of tubulin to TRESK loop does not depend on a single short determinant in the sequence, but there are multiple (at least two) contact points between the two proteins."
24830385
reach
"We provided evidence suggesting that the PKA dependent docking of 14-3-3 interfered with the binding of tubulin to TRESK."
24830385
sparser
"In order to further verify and also statistically evaluate the binding of tubulin to the cytoplasmic loop of TRESK, we performed four pairs of independent pull-down assays from mouse brain cytosol with either the bait protein (fragment 174–280) or only the control resin."
24830385
sparser
"The architectural complexity level of tubulin (e.g. monomer, dimer, oligomer, protofilament, microtubule) interacting with TRESK also has not yet been defined."
24830385
sparser
"We provided evidence suggesting that the PKA-dependent docking of 14-3-3 interfered with the binding of tubulin to TRESK."
24830385
sparser
"Although tubulin binds to TRESK in vitro , it remains to be established whether the two proteins also interact in the living cell."
24830385
sparser
"The most plausible explanation of this result is that the functional unit of tubulin, the α–β heterodimer associates to TRESK."
24830385
sparser
"Therefore, we initially tested the binding of tubulin to TRESK loop, if this serine was or was not phosphorylated with protein kinase A before the usual pull-down assay."
24830385
sparser
"In addition to the known TRESK-interacting proteins (calcineurin and 14-3-3), we detected substantial binding of tubulin to the cytoplasmic loop of TRESK."
24830385
sparser
"The persistent binding of tubulin to TRESK loop during the long washing step and NaCl gradient encouraged us to also demonstrate the interaction in pull-down assays."
24830385
sparser
"Our results also hint at the possibility that the interaction between TRESK and tubulin is conditional."
24830385
reach
"Our results also hint at the possibility that the interaction between TRESK and tubulin is conditional."
24830385
sparser
"In the following experiments we examined the interaction between TRESK loop and tubulin in a different experimental context."
24830385
reach
"P2X2 channel and TRESK may bind tubulin with a similar mechanism."
24830385
sparser
"Therefore we concluded that fragment 256–271 is a major determinant of the interaction of tubulin with the cytoplasmic loop of TRESK."
24830385
reach
"The cytoplasmic loop of the distantly related Danio rerio (zebrafish) TRESK (amino acids 174-284) also binds tubulin (as a GST-fusion protein, XREF_FIG, compare lane 3 to lanes 1 and 2)."
24830385
reach
"Although tubulin binds to TRESK in vitro, it remains to be established whether the two proteins also interact in the living cell."
24830385
sparser
"Together with the mass spectrometry data of the corresponding band from affinity chromatography, we consider it as proof that the cytoplasmic loop of TRESK interacted with tubulin in the pull-down assays."
24830385
sparser
"In fact, the reduced interaction of TRESK loop with tubulin could have been caused by either the binding of 14-3-3 to the loop or the phosphorylation of the 14-3-3-binding site by PKA in this experiment."
24830385
sparser
"The above pharmacological and overexpression experiments did not shed light on the functional relevance of the interaction between TRESK and tubulin."
24830385
sparser
"P2X2 channel and TRESK may bind tubulin with a similar mechanism."
24830385
sparser
"The cytoplasmic loop of the distantly related Danio rerio (zebrafish) TRESK (amino acids 174–284) also binds tubulin (as a GST-fusion protein, xref , compare lane 3 to lanes 1 and 2 )."
24830385
reach
"The persistent binding of tubulin to TRESK loop during the long washing step and NaCl gradient encouraged us to also demonstrate the interaction in pull-down assays."
24830385
Tubulin binds KCNK18 and serine. 1 / 1
| 1
reach
"Therefore, we initially tested the binding of tubulin to TRESK loop, if this serine was or was not phosphorylated with protein kinase A before the usual pull-down assay."
24830385
PPP3 binds Tubulin and KCNK18. 1 / 1
| 1
sparser
"Human TRESK loop (174–280) interacted with tubulin and calcineurin (similarly to its murine counterpart), in contrast to glutathione agarose and the GST-only control ( xref , compare lane 3 to lanes 1 and 2 , tubulin is indicated with an asterisk )."
24830385
MARK2 affects KCNK18
| 4 14
MARK2 inhibits KCNK18.
| 4 7
MARK2 inhibits KCNK18. 11 / 11
| 4 7
sparser
"Since ca MARK2 inhibited TRESK but kd MARK2 did not evoke this effect, the kinase activity of MARK2 was indispensable for TRESK regulation."
22145024
reach
"TRESK Background K + Channel Is Inhibited by PAR-1 and MARK Microtubule Affinity Regulating Kinases in Xenopus Oocytes."
22145024
reach
"The discrepancy, especially the cysteine to tyrosine substitution, raised the question whether human TRESK was also inhibited by MARK2."
22145024
reach
"MARK1, MARK2 and MARK3 inhibit TRESK, but not all AMPK related kinases regulate the channel."
22145024
reach
"Microinjection of constitutively active MARK2 protein acutely inhibited TRESK, and the enzyme activity of the coexpressed kinase was required for TRESK regulation."
22145024
sparser
"MARK1, MARK2 and MARK3 inhibit TRESK, but not all AMPK-related kinases regulate the channel."
22145024
reach
"MARK2 inhibits S264E mutant mouse TRESK."
22145024
reach
"The three closely related members of the MARK family accelerated the recovery of K + current (XREF_FIG), indicating that MARK1, MARK2 and MARK3 inhibited TRESK channel."
22145024
reach
"Thus MARK2 selectively inhibits TRESK activity via the S274/276/279 cluster, but does not affect the direct recruitment of 14-3-3 to the channel."
22145024
sparser
"Thus coexpression of MARK2 inhibited TRESK under resting conditions, and dramatically accelerated the (re)phosphorylation of the channel after the calcineurin-dependent activation."
22145024
sparser
"The discrepancy, especially the cysteine to tyrosine substitution, raised the question whether human TRESK was also inhibited by MARK2."
22145024
MARK2 activates KCNK18.
| 5
MARK2 activates KCNK18. 3 / 3
| 3
reach
"MARK1, MARK2 and MARK3 accelerated the return of TRESK current to the resting state after the calcium dependent activation."
22145024
reach
"Very low amounts of MARK2 cRNA (0.16 ng/oocyte) were sufficient to significantly accelerate TRESK recovery, suggesting that the effect did not rely on massive overexpression of the kinase."
22145024
reach
"Therefore we examined whether MARK2 was able to accelerate TRESK current recovery after the more physiological, but at the same time more complex, receptor stimulation (XREF_FIG)."
22145024
MARK2 activates KCNK18-S264E. 2 / 2
| 2
reach
"Thus MARK2 accelerated the recovery of S264E mutant TRESK irrespectively of the current amplitudes."
22145024
reach
"The coexpression of MARK2 accelerated the recovery of the current of S264E mutant TRESK after the ionomycin stimulation (53 +/-7% recovery at the end of the measurement in the cells coexpressing S264E mutant TRESK with MARK2 (n = 8) vs. 12 +/-12% in the control oocytes expressing only the channel (n = 8), p < 0.02, XREF_FIG)."
22145024
MARK2 phosphorylates KCNK18.
| 2
MARK2 phosphorylates KCNK18. 2 / 2
| 2
reach
"We have previously reported that MARK2 kinase and PKA phosphorylates TRESK in vitro and in Xenopus oocytes, leading to inhibition of TRESK activity [XREF_BIBR, XREF_BIBR]."
29763475
reach
"We examined whether the intracellular loop region of TRESK was phosphorylated by MARK2 in vitro."
22145024
Calcium(2+) affects KCNK18
| 5 14
Calcium(2+) activates KCNK18.
| 5 12
Calcium(2+) activates KCNK18. 12 / 12
| 5 12
reach
"Combined extracellular application of calcium (2 mM) and the calcium-ionophore ionomycin (1 microM) activated TRESK current by 50 +/-12% (n = 6, gray control curves, XREF_FIG, for further comments on this stimulation see XREF_SUPPLEMENTARY)."
22145024
reach
"These data indicate that TRESK is activated by increased cytoplasmic calcium concentration."
14981085
reach
"TRESK is activated by the elevation of cytoplasmic calcium concentration via calcineurin in HEK293 cells."
22145024
reach
"XREF_BIBR, XREF_BIBR We did not explore further the change in the calcium pattern, but it is tempting to speculate that the TRESK activation by Ca 2+ / calcineurin XREF_BIBR, XREF_BIBR might limit depolarization and Ca 2+ influx, thus preventing excessive neuronal activation."
28937579
reach
"Thus, it could support a more robust and sustained Ca 2+ signal, via a positive feedback loop as TRESK and CRAC may support each other 's activity mutually : TRESK activation by Ca 2+ - Cn and CRAC activation by TRESK mediated hyperpolarization."
27630569
reach
"Intracellular Ca 2+ -induced activation of the TRESK channel is regulated by interaction with calcineurin and 14-3-3eta [XREF_BIBR XREF_BIBR]."
27790056
reach
"In contrast to other K 2P channels expressed in sensory neurons, TRESK is activated by intracellular calcium increases through calcineurin, thus acting as a " brake " to prevent excessive activation of sensory neurons in response to depolarizing stimuli."
23691227
reach
"TRESK is activated in a complex manner by intracellular calcium signalling."
23848401
reach
"Unlike other K2P channels, TRESK is activated by the calcium signal in heterologous expression systems."
22115960
reach
"TRESK is activated by calcium involving the calcium/calmodulin dependent protein phosphatases in cell models and has been suggested being the target of the Sichuan pepper ingredient sanshool in sensory neurons XREF_BIBR."
25551770
reach
"Elevation of the cytoplasmic Ca 2+ concentration activates TRESK."
29763475
reach
"The unique calcium dependent activation of TRESK relies on the long cytoplasmic loop of the channel, a distinguishing structural element in the K2P family XREF_BIBR."
24830385
Calcium(2+) inhibits KCNK18.
| 1
Calcium(2+) inhibits KCNK18. 1 / 1
| 1
reach
"The calcium activated TRESK K + channel may reduce the hyperexcitability in the slowly migrating front of CSD characterized by depolarization and elevated cytoplasmic calcium concentration in the neurons."
22115960
Calcium(2+) increases the amount of KCNK18.
| 1
Calcium(2+) increases the amount of KCNK18. 1 / 1
| 1
reach
"It has been shown that an increase of intracellular calcium produced by the calcium ionophore ionomycin, can produce calcineurin dependent activation of TRESK expressed in Xenopus oocytes XREF_BIBR."
22355750
MARK1 affects KCNK18
| 5 8
MARK1 inhibits KCNK18.
| 1 3
MARK1 inhibits KCNK18. 4 / 4
| 1 3
reach
"The three closely related members of the MARK family accelerated the recovery of K + current (XREF_FIG), indicating that MARK1, MARK2 and MARK3 inhibited TRESK channel."
22145024
reach
"TRESK Background K + Channel Is Inhibited by PAR-1 and MARK Microtubule Affinity Regulating Kinases in Xenopus Oocytes."
22145024
reach
"MARK1, MARK2 and MARK3 inhibit TRESK, but not all AMPK related kinases regulate the channel."
22145024
sparser
"MARK1, MARK2 and MARK3 inhibit TRESK, but not all AMPK-related kinases regulate the channel."
22145024
MARK1 binds KCNK18.
| 2 2
KCNK18 binds MARK1. 4 / 4
| 2 2
reach
"Enzymatic interaction between MARK and TRESK is novel in the sense that no other ion channel is known to be phosphorylated by this kinase, and the connection between the functions of MARK XREF_BIBR and those of TRESK XREF_BIBR has not been suspected."
22145024
sparser
"Enzymatic interaction between MARK and TRESK is novel in the sense that no other ion channel is known to be phosphorylated by this kinase, and the connection between the functions of MARK xref and those of TRESK xref has not been suspected."
22145024
reach
"The interaction between MARK and TRESK is highly specific."
22145024
sparser
"The interaction between MARK and TRESK is highly specific."
22145024
MARK1 phosphorylates KCNK18.
| 2 1
MARK1 phosphorylates KCNK18. 3 / 3
| 2 1
sparser
"On the basis of our results, phosphorylation of other intracellular residues of TRESK by MARK kinases also can not be ruled out, however, these residues may have less impact on the channel activity."
22145024
sparser
"In summary, we have demonstrated that MARK directly phosphorylates TRESK in vitro and specifically inhibits the channel in Xenopus oocytes."
22145024
reach
"In summary, we have demonstrated that MARK directly phosphorylates TRESK in vitro and specifically inhibits the channel in Xenopus oocytes."
22145024
MARK1 activates KCNK18.
| 2
MARK1 activates KCNK18. 1 / 1
| 1
reach
"MARK1, MARK2 and MARK3 accelerated the return of TRESK current to the resting state after the calcium dependent activation."
22145024
Mutated MARK1 activates KCNK18. 1 / 1
| 1
reach
"While the constitutively active MARK mutants accelerated TRESK current recovery, the kinase-dead version failed to do so."
22145024
PPP3 affects KCNK18
| 4 11 1
PPP3 binds KCNK18.
| 1 7 1
PPP3 binds KCNK18. 6 / 6
| 1 5 1
sparser
"VIVIT peptide appears to inhibit the calcineurin–TRESK protein interaction at an NFAT-like docking site. xref , xref Superfusion of VIVIT peptide (0.3 μM, n = 6) depolarized NG neurons from 8-wk STZ-D rats ( xref ) and restored their excitability."
27475306
sparser
"Further, application of cyclosporin A or VIVIT peptide, which inhibits the interaction between calcineurin and TRESK at an NFAT-like docking site, xref reversed the abnormal electrophysiological properties of NG neurons from 8-wk STZ-D rats."
27475306
sparser
"General regulation of TRESK by calcineurin is in good accordance with the previous result that TRESK and calcineurin are associated via direct protein-protein interaction xref ."
22145024
sparser
"Coexpression of a constitutively active form of calcineurin with TRESK increased the basal background K(+) current and attenuated the response of the channel to the calcium signal, indicating that TRESK was activated by the permanent calcineurin activity."
14981085
reach
"Further, application of cyclosporin A or VIVIT peptide, which inhibits the interaction between calcineurin and TRESK at an NFAT like docking site, 23 reversed the abnormal electrophysiological properties of NG neurons from 8-wk STZ-D rats."
27475306
sparser
"In the present study we report that calcineurin also interacts with TRESK via an NFAT-like docking site, in addition to its enzymatic action."
16569637
NFAT binds PPP3 and KCNK18. 1 / 1
| 1
sparser
"When the T-cell is activated, calcineurin can bind to the NFAT-docking site of TRESK."
19852929
PPP3 binds Tubulin and KCNK18. 1 / 1
| 1
sparser
"Human TRESK loop (174–280) interacted with tubulin and calcineurin (similarly to its murine counterpart), in contrast to glutathione agarose and the GST-only control ( xref , compare lane 3 to lanes 1 and 2 , tubulin is indicated with an asterisk )."
24830385
PPP3 dephosphorylates KCNK18.
| 2
PPP3 dephosphorylates KCNK18. 2 / 2
| 2
sparser
"TREK-2 phosphorylated by PKC shows low channel activity [ xref ], whereas TRESK dephosphorylated by calcineurin shows high channel activity [ xref ]."
27382354
sparser
"The coexpression of PKC slowed down the recovery of the K+ current to the resting state after the calcineurin-dependent dephosphorylation of TRESK."
30992311
PPP3 activates KCNK18.
| 3 2
PPP3 activates KCNK18. 2 / 2
| 3 2
sparser
"TRESK expressed in Xenopus oocytes is strikingly activated by calcineurin in response to calcium mobilizing stimulation xref , xref , and it is assumed that native TRESK in neuronal cells is subject to similar regulation ( xref )."
21115349
sparser
"It has been shown that an increase of intracellular calcium produced by the calcium ionophore ionomycin, can produce calcineurin-dependent activation of TRESK expressed in Xenopus oocytes xref ."
22355750
KCNK18 affects TG
| 11
KCNK18 inhibits TG.
| 9
KCNK18 inhibits TG. 8 / 8
| 8
reach
"Thus, an increase in TRESK currents significantly inhibits AP initiation in both small IB4 negative and IB4 positive TG neurons."
24466320
reach
"Importantly, over-expression of TRESK subunits inhibits capsaicin evoked spikes in TG neurons, suggesting that a TRESK specific channel opener may exhibit analgesic effect via reducing the excitability of primary afferent neurons."
24466320
reach
"Over-expression of TRESK Subunits Reduces the Excitability of Small-diameter TG Neurons."
24466320
reach
"A major finding of this study is that over-expression of TRESK subunits substantially reduces the excitability of small-diameter TG neurons."
24466320
reach
"Importantly, an increase in TRESK channel activity effectively inhibited capsaicin evoked spikes in TG neurons."
24466320
reach
"Taken together, we conclude that over-expression of TRESK subunits reduces the excitability of small IB4 positive TG neurons mainly through increasing the current threshold for AP generation."
24466320
reach
"Importantly, over-expression of TRESK subunits inhibited capsaicin evoked spikes in TG neurons, suggesting that a TRESK specific channel opener may exhibit an analgesic effect via reducing the excitability of primary afferent neurons."
24466320
reach
"In TRESK global knockout mice, we found that ubiquitous loss of TRESK selectively increased the intrinsic excitability of small-diameter TG nociceptors without affecting DRG neuronal excitability."
31308053
Mutated KCNK18 inhibits TG. 1 / 1
| 1
reach
"Both mutant TRESK and the C110R variant reduced the endogenous TRESK currents in TG neurons, but the effect of the C110R variant was significantly smaller."
24805079
KCNK18 activates TG.
| 2
KCNK18 activates TG. 2 / 2
| 2
reach
"Another important issue we have addressed is whether TRESK modulates the response of TG neurons to a noxious stimulus."
24466320
reach
"Taken together, we conclude that over-expression of TRESK subunits significantly reduces the excitability of small IB4 negative TG neurons, causing an increase in rheobase as well as a decrease of spike number."
24466320
Arachidonic acid affects KCNK18
| 1 2 8
Arachidonic acid inhibits KCNK18.
| 1 2 7
Arachidonic acid inhibits KCNK18. 9 / 9
| 1 2 7
reach
"As expected, AA (10 microM) produced a 42.6 +/-4.2% decrease in TRESK current recorded at +20 mV (n = 14; p < 0.001; XREF_FIG)."
23691227
reach
"Similar to cloned TRESK, native TRESK was inhibited by acid and arachidonic acid (AA), but not zinc."
18190784
reach
"TRESK like currents in trigeminal neurons were additively inhibited by arachidonic acid, acidic pH and hypertonic stimulation, conditions usually found after tissue inflammation."
23691227
sparser
"Similar to cloned TRESK, native TRESK was inhibited by acid and arachidonic acid (AA), but not zinc."
18190784
reach
"It is unlikely that block of phospholipase A 2 underlies the substantive effects on TREK and TRESK channels seen here, because arachidonic acid enhances TREK (and TRAAK) channels (Fink et al., 1996; Enyedi and Czirjak, 2010) and blocks TRESK channels (Sano et al., 2003; Kang et al., 2004)."
26914156
reach
"In contrast, TRESK is inhibited by AA and docosahexaenoic acid [XREF_BIBR]."
27790056
reach
"In contrast, TRESK is inhibited by arachidonic acid, but the channel can still be modulated by mechanical stimuli."
23691227
sparser
"In contrast, TRESK is inhibited by arachidonic acid, but the channel can still be modulated by mechanical stimuli."
23691227
reach
"In contrast, TRESK channels are inhibited by low pH i and arachidonic acid [XREF_BIBR], and human (not murin) TRESK is activated by PKC [XREF_BIBR]."
27382354
Arachidonic acid decreases the amount of KCNK18.
| 1
Arachidonic acid decreases the amount of KCNK18. 1 / 1
| 1
reach
"In fact, here we show that TRESK expressed in heterologous systems is inhibited by arachidonic acid, acidic pH and by a slightly hypertonic medium in an additive manner."
23691227
Phosphatase affects KCNK18
| 10
Phosphatase activates KCNK18.
| 6
Phosphatase activates KCNK18. 6 / 6
| 6
reach
"The calcium/calmodulin dependent protein phosphatase calcineurin activates TRESK 5-15-fold in Xenopus oocytes XREF_BIBR."
22145024
reach
"The two-pore domain K (+) channel, TRESK (TWIK related spinal cord K (+) channel, KCNK18) is directly regulated by the calcium/calmodulin dependent phosphatase calcineurin and 14-3-3 adaptor proteins."
20215114
reach
"The two-pore domain K (+) channel, TRESK (TWIK related spinal cord K (+) channel) is reversibly activated by the calcium/calmodulin dependent protein phosphatase, calcineurin."
18397886
reach
"Cyclosporin A and FK506, specific inhibitors of the calcium/calmodulin dependent protein phosphatase (calcineurin), completely eliminated TRESK activation."
14981085
reach
"The two-pore domain K (+) channel, TRESK (TWIK related spinal cord K (+) channel) is activated in response to the calcium signal by the calcium/calmodulin dependent protein phosphatase, calcineurin."
16569637
reach
"Remarkably, TRESK activation is mediated by the calcium/calmodulin dependent serine/threonine phosphatase, calcineurin and inhibited by calcineurin inhibitors, such as cyclosporine A and FK506 [11]."
23541583
Phosphatase binds KCNK18.
| 2
Phosphatase binds KCNK18. 2 / 2
| 2
reach
"The calcium/calmodulin dependent protein phosphatase directly binds to the channel and activates TRESK current several-fold in Xenopus oocytes and HEK293 cells."
22145024
reach
"The direct, non catalytic protein protein interaction between TRESK and the phosphatase is a prerequisite of the regulation; the experimental elimination of this interaction completely prevents channel activation in response to the calcium signal (Czirjak and Enyedi, 2006a)."
22115960
Phosphatase inhibits KCNK18.
| 1
Phosphatase inhibits KCNK18. 1 / 1
| 1
reach
"The two-pore domain K (+) channel, TRESK (TWIK related spinal cord K (+) channel) is reversibly activated by the calcium/calmodulin dependent protein phosphatase, calcineurin."
18397886
Phosphatase dephosphorylates KCNK18.
| 1
Phosphatase dephosphorylates KCNK18. 1 / 1
| 1
reach
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
PKC affects KCNK18
| 3 7
PKC activates KCNK18.
| 2 6
PKC activates KCNK18. 8 / 8
| 2 6
reach
"Finally, the phorbol 12-myristate-13-acetate (PMA), a specific PKC agonist, was shown to activate TRESK channels XREF_BIBR."
24086441
sparser
"In contrast, TRESK channels are inhibited by low pH i and arachidonic acid [ xref ], and human (not murin) TRESK is activated by PKC [ xref ]."
27382354
reach
"It has recently been reported that pharmacological stimulation of protein kinase C (PKC) with the phorbol ester PMA activated human (and zebrafish but not mouse) TRESK current XREF_BIBR, XREF_BIBR."
24830385
reach
"It has recently been reported that pharmacological stimulation of protein kinase C (PKC) with the phorbol ester PMA activated human (and zebrafish but not mouse) TRESK current XREF_BIBR, XREF_BIBR."
24830385
reach
"In contrast, TRESK channels are inhibited by low pH i and arachidonic acid [XREF_BIBR], and human (not murin) TRESK is activated by PKC [XREF_BIBR]."
27382354
reach
"TRESK (K2P18.1) Background Potassium Channel is Activated by Novel-Type Protein Kinase C via Dephosphorylation."
30992311
sparser
"The enforced phosphorylation of S264 by the coexpression of a microtubule-affinity regulating kinase construct (MARK2Δ) also abolished the PKC-dependent TRESK activation."
30992311
reach
"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."
30992311
PKC dephosphorylates KCNK18.
| 1 1
PKC dephosphorylates KCNK18. 2 / 2
| 1 1
sparser
"The PKC-dependent dephosphorylation of TRESK protein was also detected by the Phos-tag SDS-PAGE method."
30992311
reach
"The PKC dependent dephosphorylation of TRESK protein was also detected by the Phos-tag SDS-PAGE method."
30992311
KCNK18 affects NRGN
| 9
KCNK18 inhibits NRGN.
| 5
KCNK18 inhibits NRGN. 5 / 5
| 5
reach
"In vivo silencing of the TRESK K + channel restores NG responsiveness to peptide stimulation and normalizes gastrointestinal functions mediated by the vago-vagal reflex in diabetic rats."
27475306
reach
"Silencing TRESK K + channels restores excitability of NG neurons of diabetic rats."
27475306
reach
"Reducing expression of the TRESK K+ channel restored NG excitability in vitro and in vivo, as well as CCK8 stimulated secretion of pancreatic enzymes and secretin induced gastrointestinal motility, which are mediated by vagovagal reflexes."
27475306
reach
"In 2 rate models of diabetes, we found that activation of the TRESK K+ channel reduced NG excitability and disrupted gastrointestinal functions."
27475306
reach
"Silencing the TRESK K + channel in the diabetic rat should restore NG excitability and improve gastrointestinal functions mediated by the vago-vagal reflex."
27475306
KCNK18 activates NRGN.
| 4
KCNK18 activates NRGN. 3 / 3
| 3
reach
"On the other hand, silencing TRESK in the NG of 8-wk STZ-D rats (n = 10) restored NG responsiveness to secretin (XREF_FIG)."
27475306
reach
"In contrast, silencing TRESK in the NG of 8-wk STZ-D rats restored NG responsiveness to CCK-8 stimulation."
27475306
reach
"Rats with NG treated with TRESK siRNA to silence the TRESK K + channel exhibited normal responses to CCK-8 and secretin stimulation (XREF_FIG)."
27475306
KCNK18 bound to PPP3 activates NRGN. 1 / 1
| 1
reach
"Further, application of cyclosporin A or VIVIT peptide, which inhibits the interaction between calcineurin and TRESK at an NFAT like docking site, 23 reversed the abnormal electrophysiological properties of NG neurons from 8-wk STZ-D rats."
27475306
P14_3_3 affects KCNK18
| 1 8
P14_3_3 binds KCNK18. 8 / 8
| 1 8
sparser
"However, this effect was demonstrated to be independent from the direct interaction between TRESK and 14-3-3 ( Czirják and Enyedi, 2010 )."
22115960
sparser
"This suggests that 14-3-3 inhibited the kinase phosphorylating the regulatory cluster of Ser-274, Ser-276, and Ser-279, independently of the direct interaction between TRESK and 14-3-3."
20215114
sparser
"The adaptor protein 14-3-3 can also bind directly to TRESK, provided that the second serine in the RSN S CPE motif (S264 in the mouse and S252 in the human channel) is phosphorylated ( Czirják et al., 2008 )."
22115960
sparser
"The binding of 14-3-3 to TRESK-loop-His 8 is in good accordance with our previous results that 14-3-3 functionally interacts with TRESK, if the channel is phosphorylated by PKA xref , xref ."
24830385
sparser
"The pull-down of tubulin was reduced by the binding of 14-3-3 to TRESK loop ( xref , lane 3 , red asterisk ), compared to the bait without the adaptor protein ( lane 2 )."
24830385
sparser
"In the present study, we report that 14-3-3 proteins directly bind to the intracellular loop of TRESK and control the kinetics of the calcium-dependent regulation of the channel."
18397886
sparser
"Serine 264 and the direct interaction of 14-3-3 with TRESK were not indispensable for the effect of MARK2, suggesting that this kinase acted via the S274/276/279 cluster."
22145024
sparser
"The association of 14-3-3 to TRESK depends on the phosphorylation of a serine ( underlined , see the above sequence) in the channel xref ."
24830385
KCNK18 affects PPP3
| 1 7 1
PPP3 binds KCNK18. 6 / 6
| 1 5 1
sparser
"VIVIT peptide appears to inhibit the calcineurin–TRESK protein interaction at an NFAT-like docking site. xref , xref Superfusion of VIVIT peptide (0.3 μM, n = 6) depolarized NG neurons from 8-wk STZ-D rats ( xref ) and restored their excitability."
27475306
sparser
"Further, application of cyclosporin A or VIVIT peptide, which inhibits the interaction between calcineurin and TRESK at an NFAT-like docking site, xref reversed the abnormal electrophysiological properties of NG neurons from 8-wk STZ-D rats."
27475306
sparser
"General regulation of TRESK by calcineurin is in good accordance with the previous result that TRESK and calcineurin are associated via direct protein-protein interaction xref ."
22145024
sparser
"Coexpression of a constitutively active form of calcineurin with TRESK increased the basal background K(+) current and attenuated the response of the channel to the calcium signal, indicating that TRESK was activated by the permanent calcineurin activity."
14981085
reach
"Further, application of cyclosporin A or VIVIT peptide, which inhibits the interaction between calcineurin and TRESK at an NFAT like docking site, 23 reversed the abnormal electrophysiological properties of NG neurons from 8-wk STZ-D rats."
27475306
sparser
"In the present study we report that calcineurin also interacts with TRESK via an NFAT-like docking site, in addition to its enzymatic action."
16569637
NFAT binds PPP3 and KCNK18. 1 / 1
| 1
sparser
"When the T-cell is activated, calcineurin can bind to the NFAT-docking site of TRESK."
19852929
PPP3 binds Tubulin and KCNK18. 1 / 1
| 1
sparser
"Human TRESK loop (174–280) interacted with tubulin and calcineurin (similarly to its murine counterpart), in contrast to glutathione agarose and the GST-only control ( xref , compare lane 3 to lanes 1 and 2 , tubulin is indicated with an asterisk )."
24830385
LPA affects KCNK18
| 7
LPA activates KCNK18.
| 6
LPA activates KCNK18. 6 / 6
| 6
reach
"In the present study we use heterologous gene expression to show that LPA strongly activates TRESK channels by its Galphaq coupled receptors."
26224542
reach
"As TRESK channels and TRPV1 receptors are both activated by LPA we next investigated LPA induced effects in the same oocyte co-injected with TRPV1 and TRESK cRNA."
26224542
reach
"Increasing LPA concentrations augmented TRESK current amplitude with an EC 50 of 0.2 muM (XREF_FIG)."
26224542
reach
"Pre-incubation of oocytes in a solution containing U73122 significantly reduced LPA mediated TRESK augmentation to 0.4 +/-0.12 fold (n = 6, two tailed unpaired t-test, p = 0.006; XREF_FIG, middle trace)."
26224542
reach
"To confirm a Galphaq coupled signalling pathway of LPA induced augmentation of TRESK currents we used the specific blocker of phospholipase C (PLC) U73122."
26224542
reach
"Upon co-expression in Xenopus oocytes LPA simultaneously increased both depolarising TRPV1 and hyperpolarising TRESK currents."
26224542
LPA inhibits KCNK18.
| 1
LPA inhibits KCNK18. 1 / 1
| 1
reach
"Now application of 2muM LPA totally abolished TRESK current augmentation (n = 12; XREF_FIG, lower trace) indicating that this step of signal transduction is essential to regulate TRESK channels by endogenous LPA receptors."
26224542
Isoflurane affects KCNK18
| 1 4
Isoflurane activates KCNK18. 5 / 5
| 1 4
sparser
"Human TRESK is potently activated by halothane, isoflurane, sevoflurane, and desflurane, making it the most sensitive volatile anesthetic-activated K2P channel yet described."
16192517
reach
"XREF_BIBR TRESK currents are increased up to 3-fold by clinical concentrations of isoflurane, halothane, sevoflurane, and desflurane."
26256973
reach
"In the Xenopus oocyte and COS-7 cell expression systems, clinical doses of isoflurane, halothane, sevoflurane, and desflurane strongly increase TRESK currents up to three-fold by increasing the open probability [XREF_BIBR]."
29948841
reach
"Human TRESK is potently activated by halothane, isoflurane, sevoflurane, and desflurane, making it the most sensitive volatile anesthetic activated K2P channel yet described."
16192517
reach
"With both whole-cell voltage-clamp and patch-clamp recording, TRESK currents increased up to three-fold by clinical concentrations of isoflurane, halothane, sevoflurane, and desflurane."
15562060
Lamotrigine affects KCNK18
| 4
Lamotrigine inhibits KCNK18. 4 / 4
| 4
reach
"Lamotrigine inhibits TRESK regulated by G protein coupled receptor agonists."
18190784
reach
"The glutamate activated TRESK was blocked by lamotrigine in DRG neurons."
18190784
reach
"In COS-7 cells transfected with mouse TRESK, 30 microM lamotrigine inhibited TRESK by approximately 50%."
18190784
reach
"As previously described [XREF_BIBR], lamotrigine 100 muM also blocked TRESK mediated background currents by 46.9 +/- 8.1% (p < 0.01; n = 6)."
21527011
Bupropion affects KCNK18
| 4
Bupropion inhibits KCNK18. 4 / 4
| 4
reach
"Acetaminophen, ibuprofen, nabumetone, and bupropion inhibited TRESK, but had no effect on TREK-2."
27382354
reach
"Bupropion blocks K ATP channel as well as TRESK [XREF_BIBR]."
27382354
reach
"Bupropion, a specific dopamine reuptake inhibitor, had no effect on TREK-2, but inhibited TRESK currents by 30 +/-17%."
27382354
reach
"The IC 50 for inhibition of TRESK by bupropion was 160 +/-17 microM (XREF_FIG)."
27382354
PPY affects KCNK18
| 4
PPY inhibits KCNK18. 4 / 4
| 4
reach
"Arachidonic acid plus mechanical stimulation of TRESK currents due to the hypertonic medium produced a maximum current inhibition of 72.7 +/-4.5% (n = 10; p < 0.001; XREF_FIG), while acidic pH and hypertonic medium decreased TRESK current by 64.6 +/-3.0% (n = 6; p < 0.05; XREF_FIG)."
23691227
reach
"In contrast, TRESK channels are inhibited by low pH i and arachidonic acid [XREF_BIBR], and human (not murin) TRESK is activated by PKC [XREF_BIBR]."
27382354
reach
"In the presence of AA, a drop in pH (pH 7.4 to 6.0) produced a further decrease in TRESK current (71.9 +/-5.2% vs. baseline current; p < 0.05), showing that the effects were additive."
23691227
reach
"TRESK like currents in trigeminal neurons were additively inhibited by arachidonic acid, acidic pH and hypertonic stimulation, conditions usually found after tissue inflammation."
23691227
PMAIP1 affects KCNK18
| 4
PMAIP1 activates KCNK18. 4 / 4
| 4
sparser
"PMA activates TRESK via protein kinase C activation and demonstrates that at least part of the native regulation of TRESK is preserved in the U20S system."
24383077
sparser
"Independent of the calcineurin pathway and independent of protein kinase A (which phosphorylates TRESK and restores baseline) is the PMA induced activation of TRESK, which occurs via protein kinase C [12] ."
24383077
sparser
"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."
30992311
sparser
"For TRESK maximal PMA activation was 1.39 ( ±0.01) fold over baseline with a pEC50 of 8.22 ( ±0.28) ( Fig. 3 )."
28882594
PKA affects KCNK18
| 1 3
PKA phosphorylates KCNK18.
| 1
PKA phosphorylates KCNK18. 1 / 1
| 1
reach
"We have previously reported that MARK2 kinase and PKA phosphorylates TRESK in vitro and in Xenopus oocytes, leading to inhibition of TRESK activity [XREF_BIBR, XREF_BIBR]."
29763475
PKA inhibits KCNK18.
| 1
PKA inhibits KCNK18. 1 / 1
| 1
reach
"Phosphorylation by MARK and PKA in the two distinct sites caused TRESK inhibition."
25866806
PKA binds KCNK18.
| 1
PKA binds KCNK18. 1 / 1
| 1
sparser
"The proteins binding to the PKA-phosphorylated TRESK loop are shown in xref as the P1 and P2 lanes representing two independent experiments."
24830385
PKA activates KCNK18.
| 1
PKA activates KCNK18-S276E. 1 / 1
| 1
reach
"The phosphorylation of Ser 264 by protein kinase A accelerated the return of the current of S276E mutant TRESK to the resting state after the calcineurin dependent activation."
20215114
MARK3 affects KCNK18
| 1 3
MARK3 inhibits KCNK18.
| 1 2
MARK3 inhibits KCNK18. 3 / 3
| 1 2
sparser
"MARK1, MARK2 and MARK3 inhibit TRESK, but not all AMPK-related kinases regulate the channel."
22145024
reach
"The three closely related members of the MARK family accelerated the recovery of K + current (XREF_FIG), indicating that MARK1, MARK2 and MARK3 inhibited TRESK channel."
22145024
reach
"MARK1, MARK2 and MARK3 inhibit TRESK, but not all AMPK related kinases regulate the channel."
22145024
MARK3 activates KCNK18.
| 1
MARK3 activates KCNK18. 1 / 1
| 1
reach
"MARK1, MARK2 and MARK3 accelerated the return of TRESK current to the resting state after the calcium dependent activation."
22145024
KCNK18 affects MCF2L2
| 4
KCNK18 inhibits MCF2L2.
| 3
KCNK18 inhibits MCF2L2. 3 / 3
| 3
reach
"TRESK channels activated by the inflammatory mediator (lysophosphatidic acid) reduce nociceptive signaling in DRG neurons [XREF_BIBR]."
27382354
reach
"In the present study, therefore, we examined whether the activation of TRESK detected by TRESK mRNA and protein by the TRESK gene recombinant adenovirus vector inhibits the capsaicin evoked SP release in DRG neurons."
22307830
reach
"TRESK knockout enhances DRG neuron excitability, and a dominant negative TRESK mutation is implicated in migraine."
22273507
KCNK18 activates MCF2L2.
| 1
KCNK18 activates MCF2L2. 1 / 1
| 1
reach
"In the present study, the TRESK gene adenovirus vector significantly enhanced the TRESK mRNA and protein of the cultured rat DRG neurons."
22307830
KCNK18 affects MARK1
| 2 2
KCNK18 binds MARK1. 4 / 4
| 2 2
reach
"Enzymatic interaction between MARK and TRESK is novel in the sense that no other ion channel is known to be phosphorylated by this kinase, and the connection between the functions of MARK XREF_BIBR and those of TRESK XREF_BIBR has not been suspected."
22145024
sparser
"Enzymatic interaction between MARK and TRESK is novel in the sense that no other ion channel is known to be phosphorylated by this kinase, and the connection between the functions of MARK xref and those of TRESK xref has not been suspected."
22145024
reach
"The interaction between MARK and TRESK is highly specific."
22145024
sparser
"The interaction between MARK and TRESK is highly specific."
22145024
2-(3,4-dimethoxyphenyl)-5-\{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino\}-2-(propan-2-yl)pentanenitrile affects KCNK18
| 1 3
2-(3,4-dimethoxyphenyl)-5-\{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino\}-2-(propan-2-yl)pentanenitrile inhibits KCNK18. 4 / 4
| 1 3
reach
"In TG neurons, verapamil (10 & mu; M) inhibited TRESK channel activity by approximately 76%."
29973548
sparser
"Verapamil Inhibits TRESK (K"
29973548
reach
"These findings show that verapamil inhibits the TRESK current independently of the blockade of Ca 2+ influx in TG neurons."
29973548
reach
"Verapamil Inhibits TRESK (K"
29973548
Zinc atom affects KCNK18
| 3
Zinc atom inhibits KCNK18.
| 2
Zinc atom inhibits KCNK18. 2 / 2
| 2
reach
"Whereas both Zn2+ and Hg2+ were selective blockers of TRESK among the mouse 2PK+ channels, human TRESK was resistant to Zn2+; it was blocked only by Hg2+."
16354767
reach
"Thus, both Zn2+ and Hg2+ are expected to inhibit endogenous TRESK in isolated mouse cells, and these ions can be applied to identify the calcineurin activated 2PK+ channel in its natural environment."
16354767
Zinc atom decreases the amount of KCNK18.
| 1
Zinc atom decreases the amount of KCNK18. 1 / 1
| 1
reach
"Mouse TRESK expressed in COS-7 cells was also inhibited by Zn2+ and Hg2+, and TRESK single-channel current was diminished in outside-out patches, indicating that the action of the ions was membrane delimited, most probably targeting the channel itself."
16354767
Phorbol affects KCNK18
| 3
Phorbol activates KCNK18. 3 / 3
| 3
reach
"Similarly, we were also able to observe activation using the previously described TRESK activator phorbol -12-myristate-13-acetate (PMA) [12]."
24383077
reach
"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."
30992311
reach
"Finally, the phorbol 12-myristate-13-acetate (PMA), a specific PKC agonist, was shown to activate TRESK channels XREF_BIBR."
24086441
Paracetamol affects KCNK18
| 3
Paracetamol inhibits KCNK18. 3 / 3
| 3
reach
"Acetaminophen, ibuprofen, nabumetone, and bupropion inhibited TRESK, but had no effect on TREK-2."
27382354
reach
"The IC 50 for inhibition of TRESK by acetaminophen, ibuprofen, and nabumetone was 220 +/-26 microM, 889 +/-10 microM, and 557 +/-35 microM."
27382354
reach
"As shown in XREF_FIG, acetaminophen (100 microM), ibuprofen (100 microM), and nabumetone (100 microM) inhibited TRESK by 27 +/-7%, 21 +/-9%, and 32 +/-11%, respectively, but they did not affect TREK-2."
27382354
Ibuprofen affects KCNK18
| 1 2
Ibuprofen inhibits KCNK18. 3 / 3
| 1 2
sparser
"The IC 50 for inhibition of TRESK by acetaminophen, ibuprofen, and nabumetone was 220±26 µM, 889±10 µM, and 557±35 µM."
27382354
reach
"As shown in XREF_FIG, acetaminophen (100 microM), ibuprofen (100 microM), and nabumetone (100 microM) inhibited TRESK by 27 +/-7%, 21 +/-9%, and 32 +/-11%, respectively, but they did not affect TREK-2."
27382354
reach
"Acetaminophen, ibuprofen, nabumetone, and bupropion inhibited TRESK, but had no effect on TREK-2."
27382354
Histamine affects KCNK18
| 3
Histamine activates KCNK18. 3 / 3
| 3
reach
"Histamine (100nM) augmented TRESK currents less potently 0.88 +/-0.17 fold (n = 12) in comparison to other mediators (XREF_FIG)."
26224542
reach
"Evidence that TRESK is activated by histamine [8] affords speculation that the physiological role of TRESK currents is to ' dampen ' cellular excitability in inflammatory responses.Based on the above evidence we sought to develop a cell based assay to identify TRESK activators."
24383077
reach
"The authors also discuss the coupling of TRESK to the histamine H1 receptor, mention that histamine can activate TRESK channels, and speculate that the physiological role of TRESK currents is to dampen cellular excitability in inflammatory responses when histamine or other inflammatory response modulators are released into the surrounding tissue."
21855646
Halothane affects KCNK18
| 3
Halothane activates KCNK18. 3 / 3
| 3
reach
"Although not used for migraine, volatile anesthetics, such as isoflurane and halothane increase TRESK currents up to 3-fold at their clinical concentrations."
24697223
reach
"Human TRESK is potently activated by halothane, isoflurane, sevoflurane, and desflurane, making it the most sensitive volatile anesthetic activated K2P channel yet described."
16192517
reach
"In the Xenopus oocyte and COS-7 cell expression systems, clinical doses of isoflurane, halothane, sevoflurane, and desflurane strongly increase TRESK currents up to three-fold by increasing the open probability [XREF_BIBR]."
29948841
Desflurane affects KCNK18
| 1 2
Desflurane activates KCNK18. 3 / 3
| 1 2
reach
"Human TRESK is potently activated by halothane, isoflurane, sevoflurane, and desflurane, making it the most sensitive volatile anesthetic activated K2P channel yet described."
16192517
reach
"In the Xenopus oocyte and COS-7 cell expression systems, clinical doses of isoflurane, halothane, sevoflurane, and desflurane strongly increase TRESK currents up to three-fold by increasing the open probability [XREF_BIBR]."
29948841
sparser
"Human TRESK is potently activated by halothane, isoflurane, sevoflurane, and desflurane, making it the most sensitive volatile anesthetic-activated K2P channel yet described."
16192517
KCNK18 affects apoptotic process
| 3
KCNK18 activates apoptotic process. 3 / 3
| 3
reach
"In vivo real time K + flux measurements and concurrent patch-clamp data on Jurkat cells revealed that both TRESK and K v 1.3 mediate AVD in the intrinsic apoptosis pathway, yet TRESK is transiently upregulated by apoptotic stimulus (staurosporine) and then completely inactivated in a half of hour, causing a strong membrane depolarization, whereas the K v 1.3 contribution to the K + efflux was more constant in time [XREF_BIBR]."
25866806
reach
"TRESK contributes to pain threshold changes by mediating apoptosis via MAPK pathway in the spinal cord."
27789381
reach
"Therefore, we investigated whether TRESK mediates inflammation and apoptosis by MAPK pathway in the spinal cord of NP rats."
27789381
KCNK18 affects TAC1
| 3
KCNK18 inhibits TAC1. 3 / 3
| 3
reach
"Indeed, over-expression of TRESK subunits in DRG neurons inhibits capsaicin evoked substance P release and attenuates nerve injury induced mechanical allodynia XREF_BIBR, XREF_BIBR."
24466320
reach
"In the present study, therefore, we examined whether the activation of TRESK detected by TRESK mRNA and protein by the TRESK gene recombinant adenovirus vector inhibits the capsaicin evoked SP release in DRG neurons."
22307830
reach
"On the other hand, our results are supported by previous studies showing that over-expression of TRESK subunits in DRG neurons inhibits capsaicin evoked substance P release and attenuates nerve injury induced mechanical allodynia XREF_BIBR, XREF_BIBR."
24466320
KCNK18 affects Phosphatase
| 3
KCNK18 binds Phosphatase.
| 2
Phosphatase binds KCNK18. 2 / 2
| 2
reach
"The calcium/calmodulin dependent protein phosphatase directly binds to the channel and activates TRESK current several-fold in Xenopus oocytes and HEK293 cells."
22145024
reach
"The direct, non catalytic protein protein interaction between TRESK and the phosphatase is a prerequisite of the regulation; the experimental elimination of this interaction completely prevents channel activation in response to the calcium signal (Czirjak and Enyedi, 2006a)."
22115960
KCNK18 activates Phosphatase.
| 1
KCNK18 activates Phosphatase. 1 / 1
| 1
reach
"In a previous study it has been shown that TRESK can be activated about 10-fold by the calcium/calmodulin dependent protein phosphatase calcineurin upon binding to the consensus motif PQIVID XREF_BIBR."
26224542
HRH1 affects KCNK18
| 3
HRH1 activates KCNK18. 3 / 3
| 3
sparser
"The authors also discuss the coupling of TRESK to the histamine H1 receptor, mention that histamine can activate TRESK channels, and speculate that the physiological role of TRESK currents is to dampen cellular excitability in inflammatory responses when histamine or other inflammatory response modulators are released into the surrounding tissue."
21855646
sparser
"TRESK is highly activated by Ca(2+), calcineurin, acetylcholine, and histamine which induce hypertrophy, whereas TRESK is inhibited by immunosuppressants, such as cyclosporin A and FK506."
19852929
sparser
"Evidence that TRESK is activated by histamine [8] affords speculation that the physiological role of TRESK currents is to ‘dampen’ cellular excitability in inflammatory responses."
24383077
ERVK-18 affects KCNK18
| 1 2
ERVK-18 inhibits KCNK18.
| 1 1
ERVK-18 inhibits KCNK18. 2 / 2
| 1 1
sparser
"We could hypothesize that the pharmacological inhibition of TRESK by TM in WT animals might contribute to the increased mechanical sensitivity because knocking down the channel produces a similar effect."
28937579
reach
"We could hypothesize that the pharmacological inhibition of TRESK by TM in WT animals might contribute to the increased mechanical sensitivity because knocking down the channel produces a similar effect."
28937579
ERVK-18 activates KCNK18.
| 1
ERVK-18 activates KCNK18. 1 / 1
| 1
reach
"XREF_BIBR, XREF_BIBR, XREF_BIBR In support of this role, we found an increased sensitivity to mechanical stimulation in TRESK KO animals, which is then further enhanced by TM exposure."
28937579
Cloxyquin affects KCNK18
| 3
Cloxyquin activates KCNK18. 3 / 3
| 3
reach
"Cloxyquin activates TRESK by a Ca 2+ / calcineurin independent mechanism."
28419410
reach
"Although limited pharmacological characterization has been performed to date, these data are compelling evidence that Cloxyquin is able to increase TRESK activity.The aim of this work was to identify activators of the two-pore domain potassium channel TRESK, which may be of therapeutic relevance in the treatment of migraine."
24383077
reach
"Indeed, due to its expression in the dorsal root ganglion a novel TRESK activator could also be of major therapeutic interest in the treatment of neuropathic pain and other nociceptive disorders.In conclusion, Cloxyquin is a novel activator of the two-pore domain potassium channel TRESK."
24383077
BRSK1 affects KCNK18
| 1 2
BRSK1 inhibits KCNK18. 3 / 3
| 1 2
reach
"Thus it can not be excluded that BRSK1 also inhibits TRESK."
22145024
reach
"The effect of BRSK1 on K + current recovery could not be determined in this experiment, because BRSK1 completely blocked the activation of TRESK (XREF_FIG)."
22145024
sparser
"Thus it cannot be excluded that BRSK1 also inhibits TRESK."
22145024
1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile affects KCNK18
| 3
1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile inhibits KCNK18. 3 / 3
| 3
reach
"Amitriptyline, citalopram, escitalopram, and fluoxetine significantly inhibited TREK-2 and TRESK currents in HEK cells (p < 0.05, n = 10)."
27382354
reach
"The IC 50 for inhibition of TRESK by citalopram, escitalopram, and fluoxetine was 168 +/-11 microM, 49 +/-7 microM, and 17 +/-5 microM, respectively."
27382354
reach
"Citalopram, escitalopram, and fluoxetine also inhibited TRESK currents by 30 +/-6%, 72 +/-7%, and 92 +/-10%, respectively (XREF_FIG)."
27382354
Zinc(2+) affects KCNK18
| 1 1
Zinc(2+) inhibits KCNK18. 1 / 1
| 1
reach
"Zn (2+) ions, which inhibit TRESK and TASK-3 K2P channels, decreased NT induced current."
21936876
Zinc(2+) inhibits KCNK18. 1 / 1
| 1
sparser
"Mouse TRESK expressed in COS-7 cells was also inhibited by Zn2+ and Hg2+, and TRESK single-channel current was diminished in outside-out patches, indicating that the action of the ions was membrane-delimited, most probably targeting the channel itself."
16354767
Tacrolimus (anhydrous) affects KCNK18
| 2
Tacrolimus (anhydrous) inhibits KCNK18. 2 / 2
| 2
reach
"In the present study, we found that the selective calcineurin inhibitor FK506 prevented TRESK activation in HEK293 cells."
22145024
reach
"Cyclosporin A and FK506, specific inhibitors of the calcium/calmodulin dependent protein phosphatase (calcineurin), completely eliminated TRESK activation."
14981085
Sevoflurane affects KCNK18
| 2
Sevoflurane activates KCNK18. 2 / 2
| 2
reach
"In the Xenopus oocyte and COS-7 cell expression systems, clinical doses of isoflurane, halothane, sevoflurane, and desflurane strongly increase TRESK currents up to three-fold by increasing the open probability [XREF_BIBR]."
29948841
reach
"Human TRESK is potently activated by halothane, isoflurane, sevoflurane, and desflurane, making it the most sensitive volatile anesthetic activated K2P channel yet described."
16192517
Nabumetone affects KCNK18
| 2
Nabumetone inhibits KCNK18. 2 / 2
| 2
reach
"Acetaminophen, ibuprofen, nabumetone, and bupropion inhibited TRESK, but had no effect on TREK-2."
27382354
reach
"As shown in XREF_FIG, acetaminophen (100 microM), ibuprofen (100 microM), and nabumetone (100 microM) inhibited TRESK by 27 +/-7%, 21 +/-9%, and 32 +/-11%, respectively, but they did not affect TREK-2."
27382354
Isobutanol affects KCNK18
| 2
Isobutanol inhibits KCNK18. 2 / 2
| 2
reach
"In another study rather high concentration (100 and 500 muM) of isobutylalkenyl amide (IBA) was found to inhibit TRESK."
22115960
reach
"In addition, the sanshool derivative IBA, which blocked TRESK currents in transfected HEK293 cells and DRGs, increased intracellular calcium in 49% of DRG neurons in culture."
21527011
Escitalopram affects KCNK18
| 2
Escitalopram inhibits KCNK18. 2 / 2
| 2
reach
"Citalopram, escitalopram, and fluoxetine also inhibited TRESK currents by 30 +/-6%, 72 +/-7%, and 92 +/-10%, respectively (XREF_FIG)."
27382354
reach
"Amitriptyline, citalopram, escitalopram, and fluoxetine significantly inhibited TREK-2 and TRESK currents in HEK cells (p < 0.05, n = 10)."
27382354
Cyclosporin A affects KCNK18
| 2
Cyclosporin A inhibits KCNK18.
| 1
Cyclosporin A inhibits KCNK18. 1 / 1
| 1
reach
"Cyclosporin A and FK506, specific inhibitors of the calcium/calmodulin dependent protein phosphatase (calcineurin), completely eliminated TRESK activation."
14981085
Cyclosporin A activates KCNK18.
| 1
Cyclosporin A activates KCNK18. 1 / 1
| 1
reach
"(Another inhibitor, cyclosporin A (0.5 microM) also blocked TRESK activation when endogenous muscarinic receptors were stimulated; results not shown.)"
22145024
Cloxyquin affects KCNK18
| 2
Cloxyquin activates KCNK18. 2 / 2
| 2
reach
"In a different set of experiments, background currents were enhanced by arachidonic acid, a known activator of TREK-1/TREK-2/TRAAK, or by cloxyquin, that activates TRESK, allowing us to test the effects of TM in native cells."
28937579
reach
"We have investigated the mechanism of cloxyquin mediated TRESK activation, focusing on the differences between the physiologically relevant regulatory states of the channel."
28419410
Azanide affects KCNK18
| 2
Azanide inhibits KCNK18. 2 / 2
| 2
reach
"Amide and ester local anesthetics inhibit TRESK in a concentration dependent manner but at concentrations generally larger than those that inhibit other tandem pore domain K channels."
15562060
reach
"In another study rather high concentration (100 and 500 muM) of isobutylalkenyl amide (IBA) was found to inhibit TRESK."
22115960
Amitriptyline affects KCNK18
| 2
Amitriptyline inhibits KCNK18. 2 / 2
| 2
reach
"Amitriptyline (a TCA, 30 microM) inhibited TREK-2 and TRESK currents by 71 +/-10% and 54 +/-16%, respectively."
27382354
reach
"Amitriptyline, citalopram, escitalopram, and fluoxetine significantly inhibited TREK-2 and TRESK currents in HEK cells (p < 0.05, n = 10)."
27382354
All-cis-docosa-4,7,10,13,16,19-hexaenoic acid affects KCNK18
| 1 1
All-cis-docosa-4,7,10,13,16,19-hexaenoic acid inhibits KCNK18. 2 / 2
| 1 1
sparser
"In contrast, TRESK is inhibited by AA and docosahexaenoic acid [ xref ]."
27790056
reach
"In contrast, TRESK is inhibited by AA and docosahexaenoic acid [XREF_BIBR]."
27790056
WHAMM affects KCNK18
| 2
KCNK18 binds WHAMM. 2 / 2
| 2
sparser
"Despite of the unchanged current and regulation of the channel in the presence of the microtubule stabilizing or disrupting agents in the oocytes, it is still possible that microtubules bind to TRESK but the channel activity is not influenced by this interaction."
24830385
sparser
"We also tried to detect the physical association of microtubules to TRESK loop."
24830385
TGFBR2 affects KCNK18
1 1 |
TGFBR2 binds KCNK18. 2 / 2
1 1 |
biogrid
No evidence text available
15761153
hprd
No evidence text available
15761153
TGFBR1 affects KCNK18
1 1 |
TGFBR1 binds KCNK18. 2 / 2
1 1 |
hprd
No evidence text available
15761153
biogrid
No evidence text available
15761153
PTH1R affects KCNK18
| 1 2
Mutated PTH1R activates KCNK18. 1 / 1
| 1
reach
"Coupling of the mutant PTH1R and Gly452Glu to TRESK again failed to augment TRESK currents significantly (1.08 +/-0.09 fold; n = 14)."
27898723
PTH1R activates KCNK18. 1 / 1
| 1 1
reach
"Activation of PTH1R with 100 nM PTH augmented TRESK currents by 2.62 +/-0.43 fold (XREF_FIG, upper left; p < 0.01; number of independent experiments (n), n = 17)."
27898723
NFAT affects KCNK18
| 2
NFAT binds KCNK18. 1 / 1
| 1
sparser
"The same non-catalytic surface of calcineurin is required for the association of the enzyme with NFAT or TRESK ( Li et al., 2007 )."
22115960
NFAT binds PPP3 and KCNK18. 1 / 1
| 1
sparser
"When the T-cell is activated, calcineurin can bind to the NFAT-docking site of TRESK."
19852929
MCF2L2 affects KCNK18
| 2
MCF2L2 inhibits KCNK18. 2 / 2
| 2
reach
"Enzymatic and mechanical dispersion of the DRG to yield isolated cells or axotomy of the sciatic nerve significantly reduced the level of TRESK mRNA in the neurons."
22115960
reach
"The glutamate activated TRESK was blocked by lamotrigine in DRG neurons."
18190784
KCNK18 affects WHAMM
| 2
KCNK18 binds WHAMM. 2 / 2
| 2
sparser
"Despite of the unchanged current and regulation of the channel in the presence of the microtubule stabilizing or disrupting agents in the oocytes, it is still possible that microtubules bind to TRESK but the channel activity is not influenced by this interaction."
24830385
sparser
"We also tried to detect the physical association of microtubules to TRESK loop."
24830385
KCNK18 affects TGFBR2
1 1 |
TGFBR2 binds KCNK18. 2 / 2
1 1 |
biogrid
No evidence text available
15761153
hprd
No evidence text available
15761153
KCNK18 affects TGFBR1
1 1 |
TGFBR1 binds KCNK18. 2 / 2
1 1 |
hprd
No evidence text available
15761153
biogrid
No evidence text available
15761153
KCNK18 affects NFAT
| 2
NFAT binds KCNK18. 1 / 1
| 1
sparser
"The same non-catalytic surface of calcineurin is required for the association of the enzyme with NFAT or TRESK ( Li et al., 2007 )."
22115960
NFAT binds PPP3 and KCNK18. 1 / 1
| 1
sparser
"When the T-cell is activated, calcineurin can bind to the NFAT-docking site of TRESK."
19852929
KCNK18 affects GJD2
| 2
KCNK18 decreases the amount of GJD2.
| 1
KCNK18 decreases the amount of GJD2. 1 / 1
| 1
reach
"Compared with SNI rats, intrathecal injection of TRESK gene recombinant adenovirus significantly downregulated the expression levels of Cx36 and Cx43 and suppressed the activation of gliocytes in the spinal cord, with hyperalgesia significantly reduced."
28160200
KCNK18 activates GJD2.
| 1
KCNK18 activates GJD2. 1 / 1
| 1
reach
"Furthermore, in the SNI model of neuropathic pain (NP), downregulation of TRESK in spinal cord neurons resulted in upregulation of connexin 36 (Cx36) and connexin 43 (Cx43), both being subtypes of gap junctions in the spinal cord, with gliocytes in the spinal cord activated ultimately."
28160200
KCNK18 affects GJA1
| 2
KCNK18 decreases the amount of GJA1.
| 1
KCNK18 decreases the amount of GJA1. 1 / 1
| 1
reach
"Compared with SNI rats, intrathecal injection of TRESK gene recombinant adenovirus significantly downregulated the expression levels of Cx36 and Cx43 and suppressed the activation of gliocytes in the spinal cord, with hyperalgesia significantly reduced."
28160200
KCNK18 activates GJA1.
| 1
KCNK18 activates GJA1. 1 / 1
| 1
reach
"Furthermore, in the SNI model of neuropathic pain (NP), downregulation of TRESK in spinal cord neurons resulted in upregulation of connexin 36 (Cx36) and connexin 43 (Cx43), both being subtypes of gap junctions in the spinal cord, with gliocytes in the spinal cord activated ultimately."
28160200
AristA affects KCNK18
| 2
AristA inhibits KCNK18. 2 / 2
| 2
reach
"Enhancement of TREK-1 and TREK-2 and inhibition of TRESK by AristA may contribute to therapeutically useful effects of this compound in pain."
26914156
reach
"AristA inhibits TRESK channel currents."
26914156
YpkA affects KCNK18
| 1
YpkA phosphorylates KCNK18 on S264. 1 / 1
| 1
sparser
"Protein kinase A phosphorylates S264 in mouse TRESK, but does not affect the regulatory cluster of S274, S276 and S279 residues."
22115960
Trans-aconitic acid affects KCNK18
| 1
Trans-aconitic acid inhibits KCNK18. 1 / 1
| 1
sparser
"Similar to cloned TRESK, native TRESK was inhibited by acid and arachidonic acid (AA), but not zinc."
18190784
Spadin affects KCNK18
| 1
Spadin inhibits KCNK18. 1 / 1
| 1
reach
"All these factors and the fact that the outward current activated by riluzole was strongly reduced by spadin, a drug not affecting TASK-1 nor TRESK channels [XREF_BIBR, XREF_BIBR] indicate that channels of the TREK subfamily should be mediating I Ril."
29928032
Rs140325655 affects KCNK18
| 1
Rs140325655-C110R inhibits KCNK18. 1 / 1
| 1
reach
"The rs772633496 (A34V) variant also causes a reduction in channel activity, whereas the rs140325655 (C110R) variant was found to cause a complete loss of TRESK function."
27191890
Permanent calcineurin affects KCNK18
| 1
Permanent calcineurin activates KCNK18. 1 / 1
| 1
reach
"Coexpression of a constitutively active form of calcineurin with TRESK increased the basal background K (+) current and attenuated the response of the channel to the calcium signal, indicating that TRESK was activated by the permanent calcineurin activity."
14981085
KdMARK2 affects KCNK18
| 1
KdMARK2 activates KCNK18. 1 / 1
| 1
reach
"MARK2-T208A, S212A, S400A, T539A (kdMARK2) did not accelerate TRESK recovery (XREF_FIG)."
22145024
Hsa-miR-124-3p affects KCNK18
1 |
Transcriptionally active hsa-miR-124-3p decreases the amount of KCNK18. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
18668037
Glutamate(2-) affects KCNK18
| 1
Glutamate(2-) activates KCNK18. 1 / 1
| 1
sparser
"The glutamate-activated TRESK was blocked by lamotrigine in DRG neurons."
18190784
Dopamine affects KCNK18
| 1
Dopamine activates KCNK18. 1 / 1
| 1
reach
"Bupropion, a specific dopamine reuptake inhibitor, had no effect on TREK-2, but inhibited TRESK currents by 30 +/-17%."
27382354
Carbachol affects KCNK18
| 1
Carbachol increases the amount of KCNK18. 1 / 1
| 1
reach
"When TRESK expressing HEK293 cells were stimulated by the muscarinic agonist carbachol (50 microM) via endogenous receptors, TRESK current was activated 3.9 +/-0.9-fold (n = 5, XREF_FIG)."
22145024
Capsaicin affects KCNK18
| 1
Capsaicin inhibits KCNK18. 1 / 1
| 1
reach
"The pungent substances piperine, capsaicin, 6-gingerol and polygodial inhibit the human two-pore domain potassium channels TASK-1, TASK-3 and TRESK."
24302912
Ammonia affects KCNK18
| 1
Ammonia activates KCNK18. 1 / 1
| 1
reach
"Ammonia positively modulated TRESK channels and glycine receptors."
17513636
Amide affects KCNK18
| 1
Amide inhibits KCNK18. 1 / 1
| 1
sparser
"In heterologous systems and sensory neurons, pyrethroids significantly inhibited K 2P currents, similar to hydroxy-α-sanshool, a compound extracted from Szechuan peppercorns, which inhibits TRESK, TASK-1, and TASK-3 and activates sensory neurons. xref Sanshool also inhibits Na v 1.3, Na v 1.7, and Na v 1.8, xref and the subsequent blocking effect on action potential firing is thought to mediate its analgesic effects by silencing Aδ-nociceptors. xref The synthetic alkylamide isobutylalkenyl amide, a sanshool derivative, also inhibits TRESK, activates sensory neurons, and produces tingling, numbing, and burning sensations in humans and painful behaviors in rodents. xref , xref , xref Another alkylamide insecticide, BTG502, structurally related to sanshool, inhibits Na v channels by binding to a site that overlaps with the pyrethroid-binding site. xref These different compounds exhibit characteristic somatosensory effects via their actions on both Na + and K + channels expressed in sensory neurons and resulting sensations might depend on the particular neuronal subtypes affected."
28937579
TUBB affects KCNK18
| 1
TUBB binds KCNK18. 1 / 1
| 1
reach
"The cytoplasmic loop of TRESK binds approximately equal amounts of alpha and beta tubulin."
24830385
THBD affects KCNK18
| 1
THBD inhibits KCNK18. 1 / 1
| 1
sparser
"We could hypothesize that the pharmacological inhibition of TRESK by TM in WT animals might contribute to the increased mechanical sensitivity because knocking down the channel produces a similar effect."
28937579
Stretch affects KCNK18
| 1
Stretch activates KCNK18. 1 / 1
| 1
reach
"Stretch activation of endogenous TRESK channels in trigeminal sensory neurons."
23691227
PTH affects KCNK18
| 1 1
PTH activates KCNK18. 1 / 1
| 1 1
reach
"Activation of PTH1R with 100 nM PTH augmented TRESK currents by 2.62 +/-0.43 fold (XREF_FIG, upper left; p < 0.01; number of independent experiments (n), n = 17)."
27898723
PPP6C affects KCNK18
| 1
PPP6C dephosphorylates KCNK18. 1 / 1
| 1
sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
PPP2CB affects KCNK18
| 1
PPP2CB dephosphorylates KCNK18. 1 / 1
| 1
sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
PPP2CA affects KCNK18
| 1
PPP2CA dephosphorylates KCNK18. 1 / 1
| 1
sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
PPP1CB affects KCNK18
| 1
PPP1CB dephosphorylates KCNK18. 1 / 1
| 1
sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
PPP1CA affects KCNK18
| 1
PPP1CA dephosphorylates KCNK18. 1 / 1
| 1
sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
PPM1G affects KCNK18
| 1
PPM1G dephosphorylates KCNK18. 1 / 1
| 1
sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
PPM1D affects KCNK18
| 1
PPM1D dephosphorylates KCNK18. 1 / 1
| 1
sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
PPM1B affects KCNK18
| 1
PPM1B dephosphorylates KCNK18. 1 / 1
| 1
sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
PPEF1 affects KCNK18
| 1
PPEF1 dephosphorylates KCNK18. 1 / 1
| 1
sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
PHLPP1 affects KCNK18
| 1
PHLPP1 dephosphorylates KCNK18. 1 / 1
| 1
sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
PDP2 affects KCNK18
| 1
PDP2 dephosphorylates KCNK18. 1 / 1
| 1
sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
MT1 affects KCNK18
| 1
KCNK18 binds MT1. 1 / 1
| 1
sparser
"Mutation in the gene encoding TRESK, a K2P channel, causes the formation of TRESK-MT1, the expected non-functional C-terminal truncated TRESK channel, and an additional unexpected protein, TRESK-MT2, which corresponds to a non-functional N-terminal truncated TRESK channel, through a mechanism called frameshift mutation-induced Alternative Translation Initiation (fsATI)."
31274103
MT affects KCNK18
| 1
MT phosphorylates KCNK18. 1 / 1
| 1
reach
"XREF_BIBR TRESK is phosphorylated by MT affinity regulating kinase XREF_BIBR and also responsible for the phosphorylation of tau."
26848276
ML67-33 affects KCNK18
| 1
ML67-33 activates KCNK18. 1 / 1
| 1
reach
"Importantly, ML67-33 strongly activates the three members of the TREK subfamily but not TASK-1, TASK-2, TASK-3 or TRESK [XREF_BIBR]."
29928032
MARK2-T208E affects KCNK18
| 1
MARK2-T208E activates KCNK18. 1 / 1
| 1
reach
"The coexpression of MARK2-T208E, S400A, T539A (caMARK2, XREF_FIG) accelerated the recovery of TRESK current after the ionomycin stimulation (p < 10 -5, compared to either the control oocytes expressing only TRESK (gray control curve and column, XREF_FIG) or the kdMARK2 group)."
22145024
MARK2-T208A affects KCNK18
| 1
MARK2-T208A activates KCNK18. 1 / 1
| 1
reach
"MARK2-T208A, S212A, S400A, T539A (kdMARK2) did not accelerate TRESK recovery (XREF_FIG)."
22145024
Loratadine affects KCNK18
| 1 1
Loratadine inhibits KCNK18. 1 / 1
| 1 1
reach
"In particular, antihistamine loratadine appears to block TRESK with a high affinity and does not display drastic collateral effects [XREF_BIBR]."
25866806
LPA receptor affects KCNK18
| 1
LPA receptor activates KCNK18. 1 / 1
| 1
reach
"Augmentation of TRESK currents by LPA receptor activation."
26224542
L-alanyl-L-alanine affects KCNK18
| 1
L-alanyl-L-alanine inhibits KCNK18. 1 / 1
| 1
sparser
"In contrast, TRESK is inhibited by AA and docosahexaenoic acid [ xref ]."
27790056
KCNK18 affects phorbol
| 1
KCNK18 activates phorbol. 1 / 1
| 1
reach
"Similarly, we were also able to observe activation using the previously described TRESK activator phorbol -12-myristate-13-acetate (PMA) [12]."
24383077
KCNK18 affects inflammatory response
| 1
KCNK18 activates inflammatory response. 1 / 1
| 1
reach
"Therefore, we investigated whether TRESK mediates inflammation and apoptosis by MAPK pathway in the spinal cord of NP rats."
27789381
KCNK18 affects halothane
| 1
KCNK18 activates halothane. 1 / 1
| 1
reach
"Although not used for migraine, volatile anesthetics, such as isoflurane and halothane increase TRESK currents up to 3-fold at their clinical concentrations."
24697223
KCNK18 affects capsaicin
| 1
KCNK18 inhibits capsaicin. 1 / 1
| 1
reach
"The present study was conducted to determine whether the activation of TRESK in the dorsal root ganglion (DRG) by the TRESK gene recombinant adenovirus vector inhibits the capsaicin evoked substance P (SP) release using a radioimmunoassay."
22307830
KCNK18 affects calcium(2+)
| 1
KCNK18 inhibits calcium(2+). 1 / 1
| 1
reach
"XREF_BIBR, XREF_BIBR We did not explore further the change in the calcium pattern, but it is tempting to speculate that the TRESK activation by Ca 2+ / calcineurin XREF_BIBR, XREF_BIBR might limit depolarization and Ca 2+ influx, thus preventing excessive neuronal activation."
28937579
KCNK18 affects benzocaine
| 1
KCNK18 inhibits benzocaine. 1 / 1
| 1
reach
"Mutations of the PQIVID sequence of TRESK to PQIVIA, PQIVAD, or PQAVAD increasingly deteriorated the calcium dependent activation in the listed order and correspondingly reduced the benzocaine sensitivity (a property discriminating activated channels from resting ones), when it was measured after the calcium signal in Xenopus oocytes."
16569637
KCNK18 affects Tubulin, and serine
| 1
Tubulin binds KCNK18 and serine. 1 / 1
| 1
reach
"Therefore, we initially tested the binding of tubulin to TRESK loop, if this serine was or was not phosphorylated with protein kinase A before the usual pull-down assay."
24830385
KCNK18 affects TUBB
| 1
TUBB binds KCNK18. 1 / 1
| 1
reach
"The cytoplasmic loop of TRESK binds approximately equal amounts of alpha and beta tubulin."
24830385
KCNK18 affects SCT
| 1
KCNK18 activates SCT. 1 / 1
| 1
reach
"On the other hand, silencing TRESK in the NG of 8-wk STZ-D rats (n = 10) restored NG responsiveness to secretin (XREF_FIG)."
27475306
KCNK18 affects PPY
| 1
KCNK18 activates PPY. 1 / 1
| 1
reach
"At least part of these effects could be mediated by the inhibitory effects of arachidonic acid and acidic pH on TRESK and further potentiated by the stretch-sensitivity of TRESK in the hypertonic conditions encountered in inflamed tissues."
23691227
KCNK18 affects PPP3, and Tubulin
| 1
PPP3 binds Tubulin and KCNK18. 1 / 1
| 1
sparser
"Human TRESK loop (174–280) interacted with tubulin and calcineurin (similarly to its murine counterpart), in contrast to glutathione agarose and the GST-only control ( xref , compare lane 3 to lanes 1 and 2 , tubulin is indicated with an asterisk )."
24830385
KCNK18 affects PKA
| 1
PKA binds KCNK18. 1 / 1
| 1
sparser
"The proteins binding to the PKA-phosphorylated TRESK loop are shown in xref as the P1 and P2 lanes representing two independent experiments."
24830385
KCNK18 affects Neoplasm Metastasis
| 1
KCNK18 inhibits Neoplasm Metastasis. 1 / 1
| 1
reach
"Overexpressing TRESK in DRG neurons suppressed tumor induced neuronal hyperexcitability and pain hypersensitivity in bone metastasis model rats, whereas knocking down TRESK increased neuronal hyperexcitability and pain hypersensitivity in normal rats."
30327410
KCNK18 affects NFAT, and PPP3
| 1
NFAT binds PPP3 and KCNK18. 1 / 1
| 1
sparser
"When the T-cell is activated, calcineurin can bind to the NFAT-docking site of TRESK."
19852929
KCNK18 affects Migraine with Aura
| 1
Mutated KCNK18 inhibits Migraine with Aura. 1 / 1
| 1
reach
"Nevertheless, this rare type of headache indicates that TRESK is related to migraine pathogenesis, and it is hoped that pharmacological stimulation of the channel will prevent or alleviate the symptoms also in the more frequent and general forms of the disorder.Although recent studies have emphasized the high expression and functional significance of TRESK in trigeminal sensory neurons, it is important to note that dominant negative TRESK mutation induced not only migraine headache but also aura symptoms."
22115960
KCNK18 affects MT1
| 1
KCNK18 binds MT1. 1 / 1
| 1
sparser
"Mutation in the gene encoding TRESK, a K2P channel, causes the formation of TRESK-MT1, the expected non-functional C-terminal truncated TRESK channel, and an additional unexpected protein, TRESK-MT2, which corresponds to a non-functional N-terminal truncated TRESK channel, through a mechanism called frameshift mutation-induced Alternative Translation Initiation (fsATI)."
31274103
KCNK18 affects KCN
| 1
KCNK18 inhibits KCN. 1 / 1
| 1
reach
"Pseudogene KCNK18 inactivates the potassium channel subfamily K member 18, which may help trigger pain centers in the brain and cause severe headaches [XREF_BIBR, XREF_BIBR]."
23587058
KCNK18 affects ERK
| 1
KCNK18 leads to the dephosphorylation of ERK. 1 / 1
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"Intrathecal injections of TRESK overexpressing adenovirus alleviated mechanical allodynia, inhibited phosphorylation of extracellular signal regulated kinase (ERK) and p38, and decreased inflammatory reactions and apoptosis in the spinal cords of SNI rats."
27789381
KCNK18 affects ATP1A2
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KCNK18 binds ATP1A2. 1 / 1
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sparser
"TRESK is associated with migraine [ xref xref xref ]."
27382354
K affects KCNK18
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K inhibits KCNK18. 1 / 1
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"In heterologous systems and sensory neurons, pyrethroids significantly inhibited K 2P currents, similar to hydroxy-alpha-sanshool, a compound extracted from Szechuan peppercorns, which inhibits TRESK, TASK-1, and TASK-3 and activates sensory neurons."
28937579
Gly-Gln affects KCNK18
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Gly-Gln activates KCNK18. 1 / 1
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"Gq protein coupled receptor agonists stimulate TRESK current 5-15-fold in Xenopus oocytes."
22115960
GS26575 affects KCNK18
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GS26575 activates KCNK18. 1 / 1
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"M1 cholinergic receptors potentiate TRESK currents up to 5-fold through an intracellular pathway including phospholipase C, calcium and calcineurin XREF_BIBR."
26224542
G alphaq -coupled receptors affects KCNK18
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G alphaq -coupled receptors activates KCNK18. 1 / 1
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"TRESK currents are activated by G alphaq -coupled receptors via a phospholipase C dependent pathway in a Ca 2+ -dependent manner."
27898723
FSK affects KCNK18
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FSK inhibits KCNK18. 1 / 1
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"Indeed, it is well known that FSK directly blocks a variety of cloned K + channels including the Kv1.1 and Kv1.4 alpha subunits [XREF_BIBR], a Na + -activated K + channel [XREF_BIBR] and the TRESK background K + channel [XREF_BIBR]."
25962132
FSCN1 affects KCNK18
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FSCN1 increases the amount of KCNK18. 1 / 1
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"In conclusion, We have demonstrated that SNL upregulates TRESK expression in the dorsal horn and increases pain sensitivity and painful animal behavior."
26256973
F139wfsX24 mutation affects KCNK18
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F139wfsX24 mutation activates KCNK18. 1 / 1
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"186 The F139wfsX24 mutation leads to a prematurely truncated and non functional TRESK channel that can also suppress wild-type channel function through a dominant negative fashion."
24697223
EDNRA affects KCNK18
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EDNRA activates KCNK18. 1 / 1
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"We show that TRESK is activated by the coexpression of the novel-type PKC isoforms eta and epsilon."
30992311
DUSP1 affects KCNK18
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DUSP1 dephosphorylates KCNK18. 1 / 1
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sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
CTDNEP1 affects KCNK18
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CTDNEP1 dephosphorylates KCNK18. 1 / 1
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sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
CDC14B affects KCNK18
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CDC14B dephosphorylates KCNK18. 1 / 1
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sparser
"This is due to stimulation of the protein phosphatase, calcineurin, which dephosphorylates TRESK channels and enhances their activity."
17068099
CABIN1 affects KCNK18
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CABIN1 activates KCNK18. 1 / 1
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"In the present study, we found that the selective calcineurin inhibitor FK506 prevented TRESK activation in HEK293 cells."
22145024
ATP1A2 affects KCNK18
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KCNK18 binds ATP1A2. 1 / 1
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sparser
"TRESK is associated with migraine [ xref xref xref ]."
27382354
AQAP mutation affects KCNK18
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AQAP mutation inhibits KCNK18. 1 / 1
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"This indicates that the AQAP mutation diminished the sensitivity of TRESK to calcium."
25202008
6-gingerol affects KCNK18
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6-gingerol inhibits KCNK18. 1 / 1
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"The pungent substances piperine, capsaicin, 6-gingerol and polygodial inhibit the human two-pore domain potassium channels TASK-1, TASK-3 and TRESK."
24302912
14-3-3 adaptor protein affects KCNK18
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14-3-3 adaptor protein activates KCNK18. 1 / 1
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"Phosphorylation dependent anchorage of 14-3-3 adaptor protein also modulates TRESK at this location."
24830385
100muM AristA affects KCNK18
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100muM AristA inhibits KCNK18. 1 / 1
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"This is illustrated for an exemplar cell in Figure XREF_FIG D. Inhibition of TRESK by 100muM AristA was 96 +/-6% (n = 6) at -60 mV, which was significantly larger than the 56 +/-5% (n = 6) inhibition seen at +20 mV in the same cells."
26914156