Ask about this productRelated genes to: KCNK6 Blocking Peptide
- Gene:
- KCNK6 NIH gene
- Name:
- potassium two pore domain channel subfamily K member 6
- Previous symbol:
- -
- Synonyms:
- K2p6.1, TWIK-2
- Chromosome:
- 19q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-04-07
- Date modifiied:
- 2016-10-11
Related products to: KCNK6 Blocking Peptide
Related articles to: KCNK6 Blocking Peptide
- Insufficient lymphocyte infiltration in the tumor microenvironment is a major cause of resistance to immunotherapy. Previous studies have indicated that NLRP3 inflammasome activation is crucial for lymphocyte infiltration and activation, but safe, effective, and specific NLRP3 inflammasome agonists are still lacking. Here, we identified a clinical phase II drug, bafetinib, that specifically activates the NLRP3 inflammasome through high-throughput drug screening. Bafetinib directly targets and binds to the potassium channel KCNK6/TWIK2, blocking its degradation via the chaperone-mediated autophagy (CMA) pathway to promote potassium efflux, thereby triggering NLRP3 inflammasome activation. Furthermore, we developed a hypoxia-responsive nanoparticle platform capable of targeted delivery of bafetinib (Baf@NPs) to tumors and specific release in the tumor microenvironment. Baf@NPs treatment significantly represses tumor growth and enhances anti-tumor immunity by triggering NLRP3 inflammasome in macrophage. Moreover, the combination of Baf@NPs with PDCD1/PD-1 antibodies further enhanced anti-tumor immunity and improved tumor treatment. Together, our results identify a safe, highly effective and specific NLRP3 inflammasome agonist and underscore it enhances anti-tumor immunity by triggering the NLRP3 inflammasome in macrophages, providing a potential therapeutic strategy for tumor treatment. 3-MA: 3-methyladenine; BMDMs: bone marrow-derived macrophage; CMA: chaperone-mediated autophagy; CHX: cycloheximide; CQ: chloroquine; Co-IP: co-immunoprecipitation; DAPI: 4',6-diamidino-2-phenylindole; TNF/TNF-α: tumor necrosis factor; HSPA8/HSC70: heat shock protein family A (Hsp70) member 8; IL1B/IL-1β: interleukin 1 beta; IL6: interleukin 6; KFERQ: lysine-phenylalanine-glutamate-arginine-glutamine; LAMP2A: lysosomal associated membrane protein 2A; LPS: lipopolysaccharide; MG132: carbobenzoxy-L-leucyl-L-leucyl-L-leucinal; NLRP3: NLR family pyrin domain containing 3; siRNAs: small interfering RNAs; WT: wild-type. - Source: PubMed
Publication date: 2026/04/12
Liu DidiJin XiangyuZeng YaoZhou XinruWang MinyuShen HuiHuang Yi - The Tandem of pore domain in a Weak Inward Rectifying K channel 2 (TWIK-2; KCNK6) is a member of the Two-Pore Domain K (K) channel family, which is associated with pulmonary hypertension, lung injury, and inflammation. Despite its physiological relevance, the structure, regulatory mechanisms, and selective modulators of TWIK-2 remain largely unknown. Here, we present a 3.7 Å single particle cryo-electron microscopy structure of human TWIK-2 and highlight its conserved and distinctive features. Using automated whole-cell patch clamp recordings, we demonstrate that gating in TWIK-2 is voltage-dependent and insensitive to changes in the extracellular pH. We identify key residues that influence TWIK-2 activity by employing site-directed mutagenesis and provide insights into the possible lipid-mediated mechanism of TWIK-2 regulation. Additionally, we demonstrate the application of high-throughput automated whole-cell patch clamp platforms to screen small molecule modulators of TWIK-2. Our work serves as a foundation for designing high-throughput small molecule screening campaigns to identify specific high-affinity TWIK-2 modulators, including promising- anti-inflammatory therapeutics. - Source: PubMed
Publication date: 2026/01/31
Ma QianqianHernandez Ciria CNavratna VikasKumar ArvindRana Jaimin KZong JiamengLee AbrahamMosalaganti Shyamal - Bladder cancer (BLCA) has a poor prognosis and continues to pose a significant challenge for clinicians. Prior studies have demonstrated a close relationship of BLCA with macrophages. However, the key subpopulations and molecular functions of macrophages in BLCA have not been uncovered. It becomes possible to use single-cell sequencing technology to explore macrophage heterogeneity and identify new biomarkers. - Source: PubMed
Publication date: 2025/10/04
Che GuangliangZhao XuejunLuo RongtuanYu QuanfengGuo XiaofengGao KeChen KangyuZhang Erfeng - Changes in extracellular matrix (ECM) and highly condensed ECM structures called perineuronal nets (PNNs) have been reported in human patients with epilepsy as well as some animal models of epilepsy. We studied potential ECM changes in a mouse model of pilocarpine-induced status epilepticus (PISE) and their potential contributions to seizures. - Source: PubMed
Publication date: 2025/06/28
Woo AnnaLin MFleischel Erik JPatel Dipan CSontheimer Harald - The (TWIK-2; KCNK6) is a member of the Two-Pore Domain K (K) channel family, which is associated with pulmonary hypertension, lung injury, and inflammation. The structure and regulatory mechanisms of TWIK-2 remain largely unknown. Here, we present the cryo-electron microscopy (cryo-EM) structure of human TWIK-2 at ~3.7 Å and highlight its conserved and unique features. Using automated whole-cell patch clamp recordings, we demonstrate that gating in TWIK-2 is voltage-dependent and insensitive to changes in the extracellular pH. We identify key residues that influence TWIK-2 activity by employing structure and sequence-guided site-directed mutagenesis and provide insights into the possible mechanism of TWIK-2 regulation. Additionally, we demonstrate the application of high-throughput automated whole-cell patch clamp platforms to screen small molecule modulators of TWIK-2. Our work serves as a foundation for designing high-throughput small molecule screening campaigns to identify specific high-affinity TWIK-2 modulators, including promising new anti-inflammatory therapeutics. - Source: PubMed
Publication date: 2025/02/24
Ma QianqianHernandez Ciria CNavratna VikasKumar ArvindLee AbrahamMosalaganti Shyamal