keyword
MENU ▼
Read by QxMD icon Read
search

WNK

keyword
https://www.readbyqxmd.com/read/28522431/wnk1-and-p38-mapk-distribution-in-ionocytes-and-accessory-cells-of-euryhaline-teleost-fish-implies-ionoregulatory-function
#1
W S Marshall, R R F Cozzi, M Spieker
Ionocytes of euryhaline teleost fish secrete NaCl, under regulation by serine and threonine kinases, including with-no-lysine kinase (WNK1) and p38 mitogen-activated protein kinase (MAPK). Mummichogs (Fundulus heteroclitus L.) were acclimated to freshwater (FW), full strength seawater (SW) and hypersaline conditions (2SW). Immunocytochemistry of ionocytes in opercular epithelia of fish acclimated to SW and 2SW revealed that WNK1-anti-pT58 phosphoantibody localized strongly to accessory cells and was present in the cytosol of ionocytes close to, cystic fibrosis transmembrane conductance regulator (CFTR) in the apical membrane and sodium, potassium, 2 chloride cotransporter (NKCC) in basolateral membrane...
May 18, 2017: Biology Open
https://www.readbyqxmd.com/read/28498874/soluble-bone-derived-osteopontin-promotes-migration-and-stem-like-behavior-of-breast-cancer-cells
#2
Graciella M Pio, Ying Xia, Matthew M Piaseczny, Jenny E Chu, Alison L Allan
Breast cancer is a leading cause of cancer death in women, with the majority of these deaths caused by metastasis to distant organs. The most common site of breast cancer metastasis is the bone, which has been shown to provide a rich microenvironment that supports the migration and growth of breast cancer cells. Additionally, growing evidence suggests that breast cancer cells that do successfully metastasize have a stem-like phenotype including high activity of aldehyde dehydrogenase (ALDH) and/or a CD44+CD24- phenotype...
2017: PloS One
https://www.readbyqxmd.com/read/28442491/constitutively-active-spak-causes-hyperkalemia-by-activating-ncc-and-remodeling-distal-tubules
#3
P Richard Grimm, Richard Coleman, Eric Delpire, Paul A Welling
Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK)...
April 25, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28414128/impaired-degradation-of-medullary-wnk4-in-the-kidneys-of-klhl2-knockout-mice
#4
Yuri Kasagi, Daiei Takahashi, Tomomi Aida, Hidenori Nishida, Naohiro Nomura, Moko Zeniya, Takayasu Mori, Emi Sasaki, Fumiaki Ando, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, Kelch-like 3 (KLHL3), and Cullin3 (CUL3) genes were identified as being responsible for hereditary hypertensive disease pseudohypoaldosteronism type II (PHAII). Normally, the KLHL3/CUL3 ubiquitin ligase complex degrades WNKs. In PHAII, the loss of interaction between KLHL3 and WNK4 increases levels of WNKs because of impaired ubiquitination, leading to abnormal over-activation of the WNK-OSR1/SPAK-NCC cascade in the kidney's distal convoluted tubules (DCT)...
April 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28389565/akt3-kinase-suppresses-pinocytosis-of-low-density-lipoprotein-by-macrophages-via-novel-wnk-sgk1-cdc42-pathway
#5
Liang Ding, Lifang Zhang, Michael Kim, Tatiana Byzova, Eugene Podrez
Fluid-phase pinocytosis of Low-density lipoprotein (LDL) by macrophages is regarded as a novel promising target to reduce macrophage cholesterol accumulation in atherosclerotic lesions. The mechanisms of regulation of fluid-phase pinocytosis in macrophages and specifically the role of Akt kinases are poorly understood. We have previously found that increased lipoprotein uptake via the receptor independent process in Akt3 kinase deficient macrophages contributes to increased atherosclerosis in Akt3-/- mice. The mechanism by which Akt3 deficiency promotes lipoprotein uptake in macrophages is unknown...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28371477/rafoxanide-and-closantel-inhibit-spak-and-osr1-kinases-by-binding-to-a-highly-conserved-allosteric-site-on-their-c-terminal-domains
#6
Mubarak A AlAmri, Hachemi Kadri, Luke J Alderwick, Nigel S Simpkins, Youcef Mehellou
SPAK and OSR1 are two protein kinases that have emerged as attractive targets in the discovery of novel antihypertensive agents due to their role in regulating electrolyte balance in vivo. Herein we report the identification of an allosteric pocket on the highly conserved C-terminal domains of these two kinases, which influences their activity. We also show that some known WNK signaling inhibitors bind to this allosteric site. Using in silico screening, we identified the antiparasitic agent rafoxanide as a novel allosteric inhibitor of SPAK and OSR1...
March 31, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28314693/wnk4-is-an-adipogenic-factor-and-its-deletion-reduces-diet-induced-obesity-in-mice
#7
Daiei Takahashi, Takayasu Mori, Eisei Sohara, Miyako Tanaka, Motoko Chiga, Yuichi Inoue, Naohiro Nomura, Moko Zeniya, Hiroki Ochi, Shu Takeda, Takayoshi Suganami, Tatemitsu Rai, Shinichi Uchida
The with-no-lysine kinase (WNK) 4 gene is a causative gene in pseudohypoaldosteronism type II. Although WNKs are widely expressed in the body, neither their metabolic functions nor their extrarenal role is clear. In this study, we found that WNK4 was expressed in mouse adipose tissue and 3T3-L1 adipocytes. In mouse primary preadipocytes and in 3T3-L1 adipocytes, WNK4 was markedly induced in the early phase of adipocyte differentiation. WNK4 expression preceded the expression of key transcriptional factors PPARγ and C/EBPα...
April 2017: EBioMedicine
https://www.readbyqxmd.com/read/28289184/renal-tubular-ubiquitin-protein-ligase-nedd4-2-is-required-for-renal-adaptation-during-long-term-potassium-depletion
#8
Lama Al-Qusairi, Denis Basquin, Ankita Roy, Renuga Devi Rajaram, Marc P Maillard, Arohan R Subramanya, Olivier Staub
Adaptation of the organism to potassium (K(+)) deficiency requires precise coordination among organs involved in K(+) homeostasis, including muscle, liver, and kidney. How the latter performs functional and molecular changes to ensure K(+) retention is not well understood. Here, we investigated the role of ubiquitin-protein ligase NEDD4-2, which negatively regulates the epithelial sodium channel (ENaC), Na(+)/Cl(-) cotransporter (NCC), and with no-lysine-kinase 1 (WNK1). After dietary K(+) restriction for 2 weeks, compared with control littermates, inducible renal tubular NEDD4-2 knockout (Nedd4L(Pax8/LC1) ) mice exhibited severe hypokalemia and urinary K(+) wasting...
March 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28282258/wnk1-is-an-unexpected-autophagy-inhibitor
#9
Sachith Gallolu Kankanamalage, A-Young Lee, Chonlarat Wichaidit, Andres Lorente-Rodriguez, Akansha M Shah, Steve Stippec, Angelique W Whitehurst, Melanie H Cobb
Autophagy is a cellular degradation pathway that is essential to maintain cellular physiology, and deregulation of autophagy leads to multiple diseases in humans. In a recent study, we discovered that the protein kinase WNK1 (WNK lysine deficient protein kinase 1) is an inhibitor of autophagy. The loss of WNK1 increases both basal and starvation-induced autophagy. In addition, the depletion of WNK1 increases the activation of the class III phosphatidylinositol 3-kinase (PtdIns3K) complex, which is required to induce autophagy...
February 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28236964/wnk-kinases-in-development-and-disease
#10
REVIEW
Aylin R Rodan, Andreas Jenny
WNK (With-No-Lysine (K)) kinases are serine-threonine kinases characterized by an atypical placement of a catalytic lysine within the kinase domain. Mutations in human WNK1 or WNK4 cause an autosomal dominant syndrome of hypertension and hyperkalemia, reflecting the fact that WNK kinases are critical regulators of renal ion transport processes. Here, the role of WNKs in the regulation of ion transport processes in vertebrate and invertebrate renal function, cellular and organismal osmoregulation, and cell migration and cerebral edema will be reviewed, along with emerging literature demonstrating roles for WNKs in cardiovascular and neural development, Wnt signaling, and cancer...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28178566/wnk-kinase-signaling-in-ion-homeostasis-and-human-disease
#11
REVIEW
Masoud Shekarabi, Jinwei Zhang, Arjun R Khanna, David H Ellison, Eric Delpire, Kristopher T Kahle
WNK kinases, along with their upstream regulators (CUL3/KLHL3) and downstream targets (the SPAK/OSR1 kinases and the cation-Cl(-) cotransporters [CCCs]), comprise a signaling cascade essential for ion homeostasis in the kidney and nervous system. Recent work has furthered our understanding of the WNKs in epithelial transport, cell volume homeostasis, and GABA signaling, and uncovered novel roles for this pathway in immune cell function and cell proliferation.
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28052988/potassium-sensing-by-renal-distal-tubules-requires-kir4-1
#12
Catherina A Cuevas, Xiao-Tong Su, Ming-Xiao Wang, Andrew S Terker, Dao-Hong Lin, James A McCormick, Chao-Ling Yang, David H Ellison, Wen-Hui Wang
The mammalian distal convoluted tubule (DCT) makes an important contribution to potassium homeostasis by modulating NaCl transport. The thiazide-sensitive Na(+)/Cl(-) cotransporter (NCC) is activated by low potassium intake and by hypokalemia. Coupled with suppression of aldosterone secretion, activation of NCC helps to retain potassium by increasing electroneutral NaCl reabsorption, therefore reducing Na(+)/K(+) exchange. Yet the mechanisms by which DCT cells sense plasma potassium concentration and transmit the information to the apical membrane are not clear...
January 4, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28052936/klhl3-knockout-mice-reveal-the-physiological-role-of-klhl3-and-the-pathophysiology-of-pseudohypoaldosteronism-type-ii-caused-by-mutant-klhl3
#13
Emi Sasaki, Koichiro Susa, Takayasu Mori, Kiyoshi Isobe, Yuya Araki, Yuichi Inoue, Yuki Yoshizaki, Fumiaki Ando, Yutaro Mori, Shintaro Mandai, Moko Zeniya, Daiei Takahashi, Naohiro Nomura, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, kelch-like 3 (KLHL3), and cullin3 (CUL3) genes are known to cause the hereditary disease pseudohypoaldosteronism type II (PHAII). It was recently demonstrated that this results from the defective degradation of WNK1 and WNK4 by the KLHL3/CUL3 ubiquitin ligase complex. However, the other physiological in vivo roles of KLHL3 remain unclear. Therefore, here we generated KLHL3(-/-) mice that expressed β-galactosidase (β-Gal) under the control of the endogenous KLHL3 promoter...
April 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28003191/calcineurin-inhibitor-cyclosporine-a-activates-renal-na-k-cl-cotransporters-via-local-and-systemic-mechanisms
#14
K I Blankenstein, A Borschewski, R Labes, A Paliege, C Boldt, J A McCormick, D H Ellison, M Bader, S Bachmann, K Mutig
Calcineurin dephosphorylates nuclear factor of activated T cells transcription factors, thereby facilitating T cell-mediated immune responses. Calcineurin inhibitors are instrumental for immunosuppression after organ transplantation but may cause side effects, including hypertension and electrolyte disorders. Kidneys were recently shown to display activation of the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb and the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule upon calcineurin inhibition using cyclosporin A (CsA)...
March 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27983989/potassium-depletion-stimulates-na-cl-cotransporter-via-phosphorylation-and-inactivation-of-the-ubiquitin-ligase-kelch-like-3
#15
Kenichi Ishizawa, Ning Xu, Johannes Loffing, Richard P Lifton, Toshiro Fujita, Shunya Uchida, Shigeru Shibata
Kelch-like 3 (KLHL3) is a component of an E3 ubiquitin ligase complex that regulates blood pressure by targeting With-No-Lysine (WNK) kinases for degradation. Mutations in KLHL3 cause constitutively increased renal salt reabsorption and impaired K(+) secretion, resulting in hypertension and hyperkalemia. Although clinical studies have shown that dietary K(+) intake affects blood pressure, the mechanisms have been obscure. In this study, we demonstrate that the KLHL3 ubiquitin ligase complex is involved in the low-K(+)-mediated activation of Na-Cl cotransporter (NCC) in the kidney...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27942049/potassium-depletion-stimulates-na-cl-cotransporter-via-phosphorylation-and-inactivation-of-the-ubiquitin-ligase-kelch-like-3
#16
Kenichi Ishizawa, Ning Xu, Johannes Loffing, Richard P Lifton, Toshiro Fujita, Shunya Uchida, Shigeru Shibata
Kelch-like 3 (KLHL3) is a component of an E3 ubiquitin ligase complex that regulates blood pressure by targeting With-No-Lysine (WNK) kinases for degradation. Mutations in KLHL3 cause constitutively increased renal salt reabsorption and impaired K(+) secretion, resulting in hypertension and hyperkalemia. Although clinical studies have shown that dietary K(+) intake affects blood pressure, the mechanisms have been obscure. In this study, we demonstrate that the KLHL3 ubiquitin ligase complex is involved in the low-K(+)-mediated activation of Na-Cl cotransporter (NCC) in the kidney...
November 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27911840/multistep-regulation-of-autophagy-by-wnk1
#17
Sachith Gallolu Kankanamalage, A-Young Lee, Chonlarat Wichaidit, Andres Lorente-Rodriguez, Akansha M Shah, Steve Stippec, Angelique W Whitehurst, Melanie H Cobb
The with-no-lysine (K) (WNK) kinases are an atypical family of protein kinases that regulate ion transport across cell membranes. Mutations that result in their overexpression cause hypertension-related disorders in humans. Of the four mammalian WNKs, only WNK1 is expressed throughout the body. We report that WNK1 inhibits autophagy, an intracellular degradation pathway implicated in several human diseases. Using small-interfering RNA-mediated WNK1 knockdown, we show autophagosome formation and autophagic flux are accelerated...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27815594/wnk-signalling-pathways-in-blood-pressure-regulation
#18
REVIEW
Meena Murthy, Thimo Kurz, Kevin M O'Shaughnessy
Hypertension (high blood pressure) is a major public health problem affecting more than a billion people worldwide with complications, including stroke, heart failure and kidney failure. The regulation of blood pressure is multifactorial reflecting genetic susceptibility, in utero environment and external factors such as obesity and salt intake. In keeping with Arthur Guyton's hypothesis, the kidney plays a key role in blood pressure control and data from clinical studies; physiology and genetics have shown that hypertension is driven a failure of the kidney to excrete excess salt at normal levels of blood pressure...
April 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27811182/leveraging-unique-structural-characteristics-of-wnk-kinases-to-achieve-therapeutic-inhibition
#19
REVIEW
Jinwei Zhang, Xianming Deng, Kristopher T Kahle
The with-no-lysine (K) WNK kinases are master regulators of the Na(+)-(K(+))-Cl(-) cotransporters, including the renal-specific NCC and NKCC2 cotransporters. The discovery of WNK463, an orally bioavailable pan-WNK kinase inhibitor that exploits unique structural properties of the WNK catalytic domain to achieve high affinity and kinase selectivity, illustrates a strategy of leveraging distinct kinase features to develop specific inhibitors and validates the genetic predictions of the in vivo pharmacology of WNK inhibition...
October 18, 2016: Science Signaling
https://www.readbyqxmd.com/read/27810492/molecular-initiating-events-of-the-intersex-phenotype-low-dose-exposure-to-17%C3%AE-ethinylestradiol-rapidly-regulates-molecular-networks-associated-with-gonad-differentiation-in-the-adult-fathead-minnow-testis
#20
April Feswick, Jennifer R Loughery, Meghan A Isaacs, Kelly R Munkittrick, Christopher J Martyniuk
Intersex, or the presence of oocytes in the testes, has been documented in fish following exposure to wastewater effluent and estrogenic compounds. However, the molecular networks underlying the intersex condition are not completely known. To address this, we exposed male fathead minnows to a low, environmentally-relevant concentration of 17alpha-ethinylestradiol (EE2) (15ng/L) and measured the transcriptome response in the testis after 96h to identify early molecular initiating events that may proceed the intersex condition...
December 2016: Aquatic Toxicology
keyword
keyword
64602
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"