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With-no-Lysine

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https://www.readbyqxmd.com/read/29667910/role-of-wnk4-and-kidney-specific-wnk1-in-mediating-the-effect-of-high-dietary-k-intake-on-romk-channel-in-the-distal-convoluted-tubule
#1
Peng Wu, Zhong-Xiuzi Gao, Xiao-Tong Su, David H Ellison, Juliette Hadchouel, Jacques Teulon, Wen-Hui Wang
With-no-lysine kinase 4 (WNK4) and kidney-Specific (KS)-WNK1 regulate ROMK (Kir1.1) channels in a variety of cell models. We now explore the role of WNK4 and KS-WNK1 in regulating ROMK in the native distal convoluted tubule (DCT)/connecting tubule (CNT) by measuring TPNQ (ROMK inhibitor)-sensitive K+ currents with whole-cell recording. TPNQ-sensitive K+ currents in DCT2/CNT of KS-WNK1-/- and WNK4-/- mice were significantly smaller than that of WT mice. In contrast, the basolateral K+ channels (a Kir4.1/5.1 heterotetramer) in the DCT were not inhibited...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29602832/intracellular-chloride-and-scaffold-protein-mo25-cooperatively-regulate-transepithelial-ion-transport-through-wnk-signaling-in-the-malpighian-tubule
#2
Qifei Sun, Yipin Wu, Sima Jonusaite, John M Pleinis, John M Humphreys, Haixia He, Jeffrey N Schellinger, Radha Akella, Drew Stenesen, Helmut Krämer, Elizabeth J Goldsmith, Aylin R Rodan
Background With No Lysine kinase (WNK) signaling regulates mammalian renal epithelial ion transport to maintain electrolyte and BP homeostasis. Our previous studies showed a conserved role for WNK in the regulation of transepithelial ion transport in the Drosophila Malpighian tubule. Methods Using in vitro assays and transgenic Drosophila lines, we examined two potential WNK regulators, chloride ion and the scaffold protein mouse protein 25 (Mo25), in the stimulation of transepithelial ion flux. Results In vitro , autophosphorylation of purified Drosophila WNK decreased as chloride concentration increased...
March 30, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29596900/role-of-nitric-oxide-and-wnk-spak-osr1-kcc2-signaling-in-daily-changes-in-gabaergic-inhibition-in-the-rat-dorsal-raphe-neurons
#3
Mi Jung Kim, Hye Jin Yang, Younghoon Kim, Insug Kang, Sung Soo Kim, Young-Wuk Cho
Serotonergic neurons in the dorsal raphe nucleus (DRN) act as wake-inducing neurons in the sleep-wake cycle and are controlled by gamma-aminobutyric acid (GABA) synaptic inputs. We investigated daily changes in GABAergic inhibition of the rat DRN neurons and the role of nitric oxide (NO) and cation-chloride co-transporters in the GABAergic action. Neuronal NO synthase (nNOS) was co-expressed in 74% of serotonergic DRN neurons and nNOS expression was higher during daytime (the sleep cycle) than that during nighttime (the wake cycle)...
March 27, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29581290/osr1-regulates-a-subset-of-inward-rectifier-potassium-channels-via-a-binding-motif-variant
#4
Clinton A Taylor, Sung-Wan An, Sachith Gallolu Kankanamalage, Steve Stippec, Svetlana Earnest, Ashesh T Trivedi, Jonathan Zijiang Yang, Hamid Mirzaei, Chou-Long Huang, Melanie H Cobb
The with-no-lysine (K) (WNK) signaling pathway to STE20/SPS1-related proline- and alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1) kinase is an important mediator of cell volume and ion transport. SPAK and OSR1 associate with upstream kinases WNK 1-4, substrates, and other proteins through their C-terminal domains which interact with linear R-F-x-V/I sequence motifs. In this study we find that SPAK and OSR1 also interact with similar affinity with a motif variant, R-x-F-x-V/I. Eight of 16 human inward rectifier K+ channels have an R-x-F-x-V motif...
April 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29576087/expression-of-oswnk9-in-arabidopsis-conferred-tolerance-to-salt-and-drought-stress
#5
Rakesh Manuka, Ankush Ashok Saddhe, Kundan Kumar
With No Lysine (WNK) kinase belongs to ser/thr protein kinase group in which conserved catalytic lysine (K) residue of subdomain II is shifted to subdomain I. In this study, we cloned full-length coding region of WNK9 from Oryza sativa (OsWNK9) and performed in silico studies to confirm the presence of all kinase signature regulatory elements. The transcript analysis revealed that OsWNK9 was strongly down regulated under salinity, drought and ABA stress in shoots. Constitutive expression of OsWNK9 in Arabidopsis thaliana imparted increased tolerance to salt, drought, and ABA stress...
May 2018: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/29563998/pdk1-wnk1-signaling-is-affected-by-hbx-and-involved-in-the-viability-and-metastasis-of-hepatic-cells
#6
Chaoying Li, Cong Lin, Xianling Cong, Ying Jiang
Hepatitis B virus (HBV)-encoded X antigen (HBx) contributes to the development of hepatocellular carcinoma (HCC). Although HBx has been implicated in the progression of HCC, its precise function in HBV-associated HCC remains unclear. In the present study, HBx affected 3-phosphoinositide-dependent protein kinase-1 (PDK1) and with-no-lysine (K) kinase (WNK1) signaling, which was identified to be involved in the viability and metastasis of hepatic cells. The phosphorylation of WNK1 was decreased when the hepatic cells were treated with a PDK1 inhibitor...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29494638/glycogen-synthase-kinase-3%C3%A3-functions-as-a-positive-effector-in-the-wnk-signaling-pathway
#7
Atsushi Sato, Hiroshi Shibuya
The with no lysine (WNK) protein kinase family is conserved among many species. Some mutations in human WNK gene are associated with pseudohypoaldosteronism type II, a form of hypertension, and hereditary sensory and autonomic neuropathy type 2A. In kidney, WNK regulates the activity of STE20/SPS1-related, proline alanine-rich kinase and/or oxidative-stress responsive 1, which in turn regulate ion co-transporters. The misregulation of this pathway is involved in the pathogenesis of pseudohypoaldosteronism type II...
2018: PloS One
https://www.readbyqxmd.com/read/29473325/cheminformatics-analysis-of-dynamic-wnk-inhibitor-interactions
#8
Melaine A Kuenemann, Denis Fourches
The With-No-Lysine (WNK) serine/threonine kinase family constitutes a unique and distinctive branch of the kinome. The four proteins of this family (WNK1/2/3/4) are involved in blood pressure regulation, body fluid, and electrolyte homeostasis. Herein, we modeled and analyzed the binding modes of all publicly-available small orthosteric and allosteric binders (including WNK463 and WNK467) experimentally tested towards any of the WNK family member. To do so, we relied on state-of-the-art cheminformatics approaches including structure-based molecular docking and molecular dynamics simulations...
February 23, 2018: Molecular Informatics
https://www.readbyqxmd.com/read/29459793/consequences-of-spak-inactivation-on-hyperkalemic-hypertension-caused-by-wnk1-mutations-evidence-for-differential-roles-of-wnk1-and-wnk4
#9
Chloé Rafael, Christelle Soukaseum, Véronique Baudrie, Perrine Frère, Juliette Hadchouel
Mutations of the gene encoding WNK1 [With No lysine (K) kinase 1] or WNK4 cause Familial Hyperkalemic Hypertension (FHHt). Previous studies have shown that the activation of SPAK (Ste20-related Proline/Alanine-rich Kinase) plays a dominant role in the development of FHHt caused by WNK4 mutations. The implication of SPAK in FHHt caused by WNK1 mutation has never been investigated. To clarify this issue, we crossed WNK1+/FHHt mice with SPAK knock-in mice in which the T-loop Thr243 residue was mutated to alanine to prevent activation by WNK kinases...
February 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29412704/with-no-lysine-kinase-4-modulates-sodium-potassium-2-chloride-cotransporter-activity-in-vivo
#10
Andrew Scott Terker, Maria Castaneda-Bueno, Mohammed Zubaerul Ferdaus, Ryan J Cornelius, Kayla J Erspamer, Xiao-Tong Su, Lauren N Miller, James A McCormick, Wen-Hui Wang, Gerardo Gamba, Chao-Ling Yang, David H Ellison
With no lysine kinase 4 (WNK4) is essential to activate the thiazide-sensitive NaCl cotransporter (NCC) along the distal convoluted tubule, an effect central to the phenotype of familial hyperkalemic hypertension. Although effects on potassium and sodium channels along the connecting and collecting tubules have also been documented, WNK4 is typically believed to have little role in modulating sodium chloride reabsorption along the thick ascending limb of the loop of Henle. Yet wnk4-/- mice (knockout mice lacking WNK4) do not demonstrate the hypocalciuria typical of pure distal convoluted tubule dysfunction...
February 7, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29392534/overexpression-of-wnk1-in-pomc-expressing-neurons-reduces-weigh-gain-via-wnk4-mediated-degradation-of-kir6-2
#11
Woo Young Chung, Jung Woo Han, Woon Heo, Min Goo Lee, Joo Young Kim
"With no lysine" (WNK) kinases have been shown to regulate various ion transporters in various tissues, but studies on the function of WNK kinases in the brain have been limited. In this study, we discovered that WNK1 and WNK4 in POMC-expressing neuronal cells in WNK1 overexpressed transgenic mice (WNK1 TG) decrease appetite via degradation of Kir6.2. Weight gain after 20 weeks of age was delayed in WNK1 TG mice as a result of reduced food intake. Expression of WNK1 and proopiomelanocortin (POMC) was higher in POMC-expressing neurons in the hypothalamus of WNK1 TG mice than in WT mice...
February 1, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29361671/mechanisms-and-controversies-in-mutant-cul3-mediated-familial-hyperkalemic-hypertension
#12
Mohammed Zubaerul Ferdaus, James A McCormick
Autosomal dominant mutations in Cullin3 (Cul3) cause the most severe form of Familial Hyperkalemic Hypertension (FHHt). Cul3 mutations cause skipping of exon 9 which results in an internal deletion of 57 amino acids from the CUL3 protein (CUL3-∆9). The precise mechanism by which this altered form of CUL3 causes FHHt is controversial. CUL3 is a member of the Cullin-Ring ubiquitin Ligase (CRL) family which mediates ubiquitination and thus degradation of cellular proteins including With-no-lysine [K] kinases (WNKs)...
January 17, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29287086/dose-duration-reciprocity-for-g-protein-activation-modulation-of-kinase-to-substrate-ratio-alters-cell-signaling
#13
Kang-Ling Liao, Charles E Melvin, Rosangela Sozzani, Roger D Jones, Timothy C Elston, Alan M Jones
In animal cells, activation of heterotrimeric G protein signaling generally occurs when the system's cognate signal exceeds a threshold, whereas in plant cells, both the amount and the exposure time of at least one signal, D-glucose, are used toward activation. This unusual signaling property called Dose-Duration Reciprocity, first elucidated in the genetic model Arabidopsis thaliana, is achieved by a complex that is comprised of a 7-transmembrane REGULATOR OF G SIGNALING (RGS) protein (AtRGS1), a Gα subunit that binds and hydrolyzes nucleotide, a Gβγ dimer, and three WITH NO LYSINE (WNK) kinases...
2017: PloS One
https://www.readbyqxmd.com/read/29237822/potassium-regulated-distal-tubule-wnk-bodies-are-kidney-specific-wnk1-dependent
#14
Cary R Boyd-Shiwarski, Daniel J Shiwarski, Ankita Roy, Hima N Namboodiri, Lubika J Nkashama, Jian Xie, Kara L McClain, Allison Marciszyn, Thomas R Kleyman, Roderick J Tan, Donna B Stolz, Manojkumar A Puthenveedu, Chou-Long Huang, Arohan R Subramanya
With-no-lysine (WNK) kinases coordinate volume and potassium homeostasis by regulating renal tubular electrolyte transport. In the distal convoluted tubule (DCT), potassium imbalance causes WNK signaling complexes to concentrate into large discrete foci, which we call "WNK bodies." Although these structures have been reported previously, the mechanisms that drive their assembly remain obscure. Here, we show that kidney-specific WNK1 (KS-WNK1), a truncated kinase-defective WNK1 isoform that is highly expressed in the DCT, is critical for WNK body formation...
February 15, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29202451/akt3-inhibits-adipogenesis-and-protects-from-diet-induced-obesity-via-wnk1-sgk1-signaling
#15
Liang Ding, Lifang Zhang, Sudipta Biswas, Rebecca C Schugar, J Mark Brown, Tatiana Byzova, Eugene Podrez
Three Akt isoforms, encoded by 3 separate genes, are expressed in mammals. While the roles of Akt1 and Akt2 in metabolism are well established, it is not yet known whether Akt3 plays a role in metabolic diseases. We now report that Akt3 protects mice from high-fat diet-induced obesity by suppressing an alternative pathway of adipogenesis via with no lysine protein kinase-1 (WNK1) and serum/glucocorticoid-inducible kinase 1 (SGK1). We demonstrate that Akt3 specifically phosphorylates WNK1 at T58 and promotes its degradation via the ubiquitin-proteasome pathway...
November 16, 2017: JCI Insight
https://www.readbyqxmd.com/read/29196535/wnk1-kinase-and-the-termination-factor-pcf11-connect-nuclear-mrna-export-with-transcription
#16
Adam Volanakis, Kinga Kamieniarz-Gdula, Margarita Schlackow, Nick J Proudfoot
Nuclear gene transcription is coordinated with transcript release from the chromatin template and messenger RNA (mRNA) export to the cytoplasm. Here we describe the role of nuclear-localized kinase WNK1 (with no lysine [K] 1) in the mammalian mRNA export pathway even though it was previously established as a critical regulator of ion homeostasis in the cytoplasm. Our data reveal that WNK1 phosphorylates the termination factor PCF11 on its RNA polymerase II (Pol II) C-terminal domain (CTD)-interacting domain (CID)...
November 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29148820/a-functional-kinase-short-interfering-ribonucleic-acid-screen-using-protease-activated-receptor-2-dependent-opening-of-transient-receptor-potential-vanilloid-4
#17
William G Darby, Megan S Grace, Kaylene J Simpson, Owen L Woodman, Peter McIntyre
Protease-activated receptor 2 (PAR2 ) is a proinflammatory G-protein coupled receptor (GPCR) that is activated by inflammatory proteases, and its activation initiates signaling pathways that modulate the nonselective cation channel transient receptor potential vanilloid-4 (TRPV4). PAR2 -dependent opening of TRPV4 has been attributed to kinase activation, but the identity of the responsible enzymes is unknown. Deciphering the signaling pathways involved in the PAR2 -dependent opening of TRPV4 may yield new targets for pain treatment...
January 2018: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/29134279/dietary-k-and-cl-independently-regulate-basolateral-conductance-in-principal-and-intercalated-cells-of-the-collecting-duct
#18
Viktor N Tomilin, Oleg Zaika, Arohan R Subramanya, Oleh Pochynyuk
The renal collecting duct contains two distinct cell types, principal and intercalated cells, expressing potassium Kir 4.1/5.1 (KCNJ10/16) and chloride ClC-K2 (ClC-Kb in humans) channels on their basolateral membrane, respectively. Both channels are thought to play important roles in controlling systemic water-electrolyte balance and blood pressure. However, little is known about mechanisms regulating activity of Kir 4.1/5.1 and ClC-K2/b. Here, we employed patch clamp analysis at the single channel and whole cell levels in freshly isolated mouse collecting ducts to investigate regulation of Kir 4...
February 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29096595/pleiotropic-actions-of-fgf23
#19
Reinhold G Erben
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone, mainly produced by osteoblasts and osteocytes in response to increased extracellular phosphate and circulating vitamin D hormone. Endocrine FGF23 signaling requires co-expression of the ubiquitously expressed FGF receptor 1 (FGFR1) and the co-receptor α-Klotho (Klotho). In proximal renal tubules, FGF23 suppresses the membrane expression of the sodium-phosphate cotransporters Npt2a and Npt2c which mediate urinary reabsorption of filtered phosphate...
October 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28969021/secreted-protein-acidic-and-rich-in-cysteine-sparc-induces-cell-migration-and-epithelial-mesenchymal-transition-through-wnk1-snail-in-non-small-cell-lung-cancer
#20
Jen-Yu Hung, Meng-Chi Yen, Shu-Fang Jian, Cheng-Ying Wu, Wei-An Chang, Kuan-Ting Liu, Ya-Ling Hsu, Inn-Wen Chong, Po-Lin Kuo
The extracellular matrix is a component of physiological microenvironment and a regulator of cellular processes such as migration and proliferation. Secreted Protein Acidic and Rich in Cysteine (SPARC/osteonectin) is an extracellular matrix-associated glycoprotein involved in the regulation of cell proliferation and cell migration in several types of cancers. However, the role of SPARC in lung cancer is paradoxical and details of the regulatory mechanism are not well-known. In this study, we investigated novel SPARC-mediated signaling pathways...
September 8, 2017: Oncotarget
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