| Downregulation of WNK4 expression facilitates the proliferation of gastric cancer cells via activation of the STAT3 signaling pathway. | Downregulation of WNK4 expression facilitates the proliferation of gastric cancer cells via activation of the STAT3 signaling pathway.
Li M, Shao X, Ning Q, Sun R, Li R, Liu Y, Yuan Y, Zhang Y. | 07/28/2024 |
| KLHL3-dependent WNK4 degradation affected by potassium through the neddylation and autophagy pathway. | KLHL3-dependent WNK4 degradation affected by potassium through the neddylation and autophagy pathway.
Ying S, Guo Q, Zhang C., Free PMC Article | 07/27/2023 |
| Identification of a novel KLHL3-interacting motif in the C-terminal region of WNK4. | Identification of a novel KLHL3-interacting motif in the C-terminal region of WNK4.
Wang L, Wu G, Peng JB. | 06/22/2023 |
| D564N mutation in WNK4 is a novel genetic cause of PHA2 with a relatively mild phenotype. | A familial case of pseudohypoaldosteronism type II (PHA2) with a novel mutation (D564N) in the acidic motif in WNK4.
Sakoh T, Sekine A, Mori T, Mizuno H, Kawada M, Hiramatsu R, Hasegawa E, Hayami N, Yamanouchi M, Suwabe T, Sawa N, Ubara Y, Fujimaru T, Sohara E, Shinichi U, Hoshino J, Takaichi K., Free PMC Article | 05/30/2020 |
| Molecular dynamics simulations indicate the effects of these mutations on the interaction between the Kelch domain of kelch-like protein 3 (KLHL3) and the acidic motif (AM) of WNK lysine deficient protein kinase 4 protein (WNK4). | Unveiling the Distinct Mechanisms by which Disease-Causing Mutations in the Kelch Domain of KLHL3 Disrupt the Interaction with the Acidic Motif of WNK4 through Molecular Dynamics Simulation.
Wang L, Jiang C, Cai R, Chen XZ, Peng JB., Free PMC Article | 02/29/2020 |
| This study has identified specific WNK4 that are involved in opening TRPV4, using a selective screen of short interfering ribonucleic acid (siRNA) SMARTpools, which individually targeted all human kinases, in human embryonic kidney 293 (HEK293) cells that stably express inducible TRPV4. | A Functional Kinase Short Interfering Ribonucleic Acid Screen Using Protease-Activated Receptor 2-Dependent Opening of Transient Receptor Potential Vanilloid-4.
Darby WG, Grace MS, Simpson KJ, Woodman OL, McIntyre P. | 11/2/2019 |
| Kidney-specific WNK1 isoform is a potent activator of WNK4 and NCC-mediated sodium/chloride transport. | Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 and NCC.
Argaiz ER, Chavez-Canales M, Ostrosky-Frid M, Rodríguez-Gama A, Vázquez N, Gonzalez-Rodriguez X, Garcia-Valdes J, Hadchouel J, Ellison D, Gamba G., Free PMC Article | 07/13/2019 |
| tacrolimus increases levels of KLHL3(S433-P), resulting in increased levels of WNK4, phosphorylated SPAK, and Na-Cl cotransporter.These findings demonstrate that KLHL3(S433-P) is a calcineurin substrate and implicate increased KLHL3 phosphorylation in tacrolimus-induced pathologies. | Calcineurin dephosphorylates Kelch-like 3, reversing phosphorylation by angiotensin II and regulating renal electrolyte handling.
Ishizawa K, Wang Q, Li J, Yamazaki O, Tamura Y, Fujigaki Y, Uchida S, Lifton RP, Shibata S., Free PMC Article | 05/4/2019 |
| 5 WNK4 sites (S47, S64, S1169, S1180, S1196) are phosphorylated downstream of AngII signaling in cultured cells and in vitro by PKC and PKA. Phosphorylation at S64 and S1196 promoted phosphorylation of the WNK4 kinase T-loop at S332 (required for kinase activation) and increased phosphorylation of SPAK. Volume depletion induced phosphorylation of these sites in vivo, predominantly in the distal convoluted tubule. | Phosphorylation by PKC and PKA regulate the kinase activity and downstream signaling of WNK4.
Castañeda-Bueno M, Arroyo JP, Zhang J, Puthumana J, Yarborough O 3rd, Shibata S, Rojas-Vega L, Gamba G, Rinehart J, Lifton RP., Free PMC Article | 05/12/2018 |
| Modulation of WNK4 activity by [Cl]i can account for its dual role on the NCC, and this has important physiological implications regarding the regulation of extracellular potassium concentration. | The regulation of Na+Cl- cotransporter by with-no-lysine kinase 4.
Argaiz ER, Gamba G. | 01/23/2018 |
| This study provides substantial new insights into the role of phosphorylation of KLHL3 in regulating the interaction with WNK4 | Phosphorylation of KLHL3 at serine 433 impairs its interaction with the acidic motif of WNK4: a molecular dynamics study.
Wang L, Peng JB., Free PMC Article | 07/15/2017 |
| The distribution of allele frequency and genotype of WNK4 gene Ala589Ser polymorphism showed significant differences between essential hypertension subjects, with or without type 2 diabetes mellitus, and normotensive subjects. | Novel Association of WNK4 Gene, Ala589Ser Polymorphism in Essential Hypertension, and Type 2 Diabetes Mellitus in Malaysia.
Ghodsian N, Ismail P, Ahmadloo S, Heidari F, Haghvirdizadeh P, Ataollahi Eshkoor S, Etemad A., Free PMC Article | 06/10/2017 |
| Data indicate that WNK lysine deficient protein kinase 4 protein (WNK4) was degraded not only by proteasomes but also by atypical protein kinase C scaffold protein p62 (p62)-kelch-like 3 protein (KLHL3)-mediated selective autophagy. | Involvement of selective autophagy mediated by p62/SQSTM1 in KLHL3-dependent WNK4 degradation.
Mori Y, Mori T, Wakabayashi M, Yoshizaki Y, Zeniya M, Sohara E, Rai T, Uchida S. | 04/2/2016 |
| this meta-analysis suggested that WNK4 G1155942T and C6749T gene polymorphisms may contribute to the susceptibility and development of hypertension. | Comprehensive assessment of the association of WNK4 polymorphisms with hypertension: evidence from a meta-analysis.
Guo XG, Ding J, Xu H, Xuan TM, Jin WQ, Yin X, Shang YP, Zhang FR, Zhu JH, Zheng LR., Free PMC Article | 03/26/2016 |
| Akt and PKA phosphorylated KLHL3 at S433, and phosphorylation of KLHL3 by PKA inhibited WNK4 degradation. | Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3.
Yoshizaki Y, Mori Y, Tsuzaki Y, Mori T, Nomura N, Wakabayashi M, Takahashi D, Zeniya M, Kikuchi E, Araki Y, Ando F, Isobe K, Nishida H, Ohta A, Susa K, Inoue Y, Chiga M, Rai T, Sasaki S, Uchida S, Sohara E. | 02/6/2016 |
| WNK4 is a substrate of SFKs and the association of c-Src and PTP-1D with WNK4 at Tyr(1092) and Tyr(1143) plays an important role in modulating the inhibitory effect of WNK4 on ROMK | Src-family protein tyrosine kinase phosphorylates WNK4 and modulates its inhibitory effect on KCNJ1 (ROMK).
Lin DH, Yue P, Yarborough O 3rd, Scholl UI, Giebisch G, Lifton RP, Rinehart J, Wang WH., Free PMC Article | 07/4/2015 |
| WNK4 inhibits SNARE formation of syntaxin 13 with VAMP2. | WNK4 inhibits plasma membrane targeting of NCC through regulation of syntaxin13 SNARE formation.
Chung WY, Park HW, Han JW, Lee MG, Kim JY. | 12/6/2014 |
| Regulation of WNK4 by CUL3 and its relationship to blood pressure regulation and electrolyte homeostasis. [Review] | Insights in cullin 3/WNK4 and its relationship to blood pressure regulation and electrolyte homeostasis.
Andérica-Romero AC, Escobar L, Padilla-Flores T, Pedraza-Chaverri J. | 11/29/2014 |
| WNK4 inhibits Large-conductance, Ca(2 )-activated K( ) channel activity, in part, by increasing channel degradation through an ubiquitin-dependent pathway. | Regulation of large-conductance Ca2+-activated K+ channels by WNK4 kinase.
Wang Z, Subramanya AR, Satlin LM, Pastor-Soler NM, Carattino MD, Kleyman TR., Free PMC Article | 12/14/2013 |
| analysis of how mutations of KLHL3 show less ability to ubiquitinate WNK4 because of KLHL3's low stability and/or decreased binding to CUL3 or WNK4 | Decrease of WNK4 ubiquitination by disease-causing mutations of KLHL3 through different molecular mechanisms.
Mori Y, Wakabayashi M, Mori T, Araki Y, Sohara E, Rai T, Sasaki S, Uchida S. | 11/16/2013 |
| WNK4 inhibits ENaC channel activity independently of Nedd4-2-mediated ENaC ubiquitination. | WNK4 inhibition of ENaC is independent of Nedd4-2-mediated ENaC ubiquitination.
Yu L, Cai H, Yue Q, Alli AA, Wang D, Al-Khalili O, Bao HF, Eaton DC., Free PMC Article | 09/7/2013 |
| KLHL3 is a substrate adaptor for WNK4 in a ubiquitin E3 ligase complex | Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation.
Wu G, Peng JB., Free PMC Article | 08/31/2013 |
| The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. | The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction.
Ohta A, Schumacher FR, Mehellou Y, Johnson C, Knebel A, Macartney TJ, Wood NT, Alessi DR, Kurz T., Free PMC Article | 05/4/2013 |
| The Exon 8 G1155942T polymorphism in WNK4 gene was associated with hypertension in the Kazakhs ethnic group in Xinjiang, and the T allele might be the risk factor for essential hypertension. | [Study on the association between genetic polymorphism on WNK4 genes and essential hypertension among Kazakhs ethnic population, in Xinjiang].
Cao FF, Han H, Wang F, Chen XD, Lu M, Wang XF, Lin RY, Wen H, Jin L. | 04/6/2013 |
| R1185C mutation disrupts a CaM binding site at the WNK4 COOH-terminal region and alters the phosphorylation of WNK4 by SGK1. | Disease-causing R1185C mutation of WNK4 disrupts a regulatory mechanism involving calmodulin binding and SGK1 phosphorylation sites.
Na T, Wu G, Zhang W, Dong WJ, Peng JB., Free PMC Article | 04/6/2013 |