anti-WNK Lysine Deficient Protein Kinase 4 (WNK4) Antibodies

Human WNK Lysine Deficient Protein Kinase 4 (WNK4) interaction partners

1. 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.

2. 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.

3. This study provides substantial new insights into the role of phosphorylation of KLHL3 in regulating the interaction with WNK4

4. 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.

5. 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.

6. this meta-analysis suggested that WNK4 G1155942T and C6749T gene polymorphisms may contribute to the susceptibility and development of hypertension.

7. Akt and PKA phosphorylated KLHL3 at S433, and phosphorylation of KLHL3 by PKA inhibited WNK4 degradation.

8. 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

9. WNK4 inhibits SNARE formation of syntaxin 13 with VAMP2.

10. Regulation of WNK4 by CUL3 and its relationship to blood pressure regulation and electrolyte homeostasis. [Review]

11. WNK4 inhibits Large-conductance, Ca(2 )-activated K( ) channel activity, in part, by increasing channel degradation through an ubiquitin-dependent pathway.

12. 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

13. WNK4 inhibits ENaC channel activity independently of Nedd4-2-mediated ENaC ubiquitination.

14. KLHL3 is a substrate adaptor for WNK4 in a ubiquitin E3 ligase complex

15. 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.

16. 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.

17. R1185C mutation disrupts a CaM binding site at the WNK4 COOH-terminal region and alters the phosphorylation of WNK4 by SGK1.

18. hypertension associated polymorphisms in WNK1 and WNK4 may not be predictors for antihypertensive response to diuretics.

19. Data show that K1169E lost its inhibitory effect on NCC surface expression compared to wild-type WNK4 when expressed in HEK293 cells, while it did not change NCC total protein expression.

20. Results show that Tyr512 phosphorylation is a novel signal regulating the prevalence of CFTR at the cell surface and that WNK4 and Syk perform an antagonistic role in this process.

Mouse (Murine) WNK Lysine Deficient Protein Kinase 4 (WNK4) interaction partners

1. C-terminally truncated WNK4 constructs are more active than full-length WNK4, as long as they contain the C-terminal SPAK-binding site.

2. reduced age-dependent weight gain of WNK1 TG mice seems to be related with the decreased Kir6.2 expression via WNK1- and WNK4-regulated protein stability of Kir6.2.

3. WNK4 protein affected the DNA-binding ability of C/EBPbeta and thereby reduced PPARgamma expression. In the WNK4(-/-) mice, PPARgamma and C/EBPalpha expression were decreased in adipose tissues, and the mice exhibited partial resistance to high-fat diet-induced adiposity.

4. However, phosphorylation of SPAK and NCC at distal convoluted tubules were almost completely absent even in WNK4(-/-)KLHL3(R528H/R528H) mice. In conclusion, increased WNK1 was unable to compensate for WNK4 deficiency and phosphorylate the NCC, indicating that WNK4 is indispensable for the onset of PHAII.

5. ENaC and ROMK channel activity in kidney tubules are inhibited in TgWnk4(pseudoaldosteronism type II) mice. Wnk4(PHAII)-induced inhibition of ENaC and ROMK may contribute to the suppression of K(+) secretion in the tubules.

6. Accordingly, medullary WNK4 protein levels were significantly increased in the kidneys of KLHL2(-/-) mice. KLHL2 is indeed a physiological regulator of WNK4 in vivo; however, its function might be different from that of KLHL3 because KLHL2 mainly localized in medulla.

7. The results indicate that quite modest changes in dietary K intake affect plasma [K] and thiazide-sensitive NaCl cotransporter activity. These effects are mediated largely by WNK4, as this kinase exhibits unique Cl-sensitive properties.

8. the increased NCC expression and activation is present in CMA which is highly associated with the enhanced WNK4-SPAK signal pathway using WNK4-/- and SPAK-/- mice.

9. increased protein expression levels of WNK1 and WNK4 kinases cause PHAII by KLHL3 R528H mutation due to impaired KLHL3-Cullin3-mediated ubiquitination.

10. KLHL3 is phosphorylated at serine 433 in the Kelch domain (a site frequently mutated in hypertension with hyperkalemia) by protein kinase C in cultured cells and that this phosphorylation prevents WNK4 binding and degradation.

11. WNK4 is the major positive regulator of NCC in the kidneys.

12. WNK1 stimulates the activity of the Na-Cl cotransporter via SPAK, an effect antagonized by WNK4.

13. in addition to SPAK and OSR1, WNK4 is able to anchor itself to the N-terminal domain of NKCC1 and to promote cotransporter activation.

14. SPAK deficiency corrects pseudohypoaldosteronism II caused by WNK4 mutation.

15. Activation of the renal Na+:Cl- cotransporter by angiotensin II is a WNK4-dependent process.

16. data suggest that WNK4 inhibits NCC protein through activating the MAPK ERK1/2 signaling pathway.

17. these results suggest that these PHAII-causing mutations disrupt a Ca(2+)-sensing mechanism around the acidic motif necessary for the regulation of WNK4 kinase activity by Ca(2+) ions.

18. Immunolocalization of WNK4 in mouse kidney.

19. Results clearly establish that PHAII caused by the WNK4 D561A mutation is dependent on the activation of the WNK-OSR1/SPAK-NCC cascade.

20. beta(2)-adrenergic receptor stimulation led to decreased transcription of the gene encoding WNK4, a regulator of sodium reabsorption