| Interacting proteins: P48048 and Q96J92 |
Pubmed |
SVM Score :0.0 |
| For example , the related kinase WNK 4 regulates the Na Cl co transporter ( NCC ) , paracellular Cl flux , and the K+ channel ROMK 1 ( Kir1 . 1 ) to maintain renal NaCl and K+ homeostasis ; mutations in PRKWNK 4 , encoding WNK 4 , cause a Mendelian disease featuring hypertension and hyperkalemia . ^^^ |
|
| Interacting proteins: P48048 and Q96J92 |
Pubmed |
SVM Score :0.0 |
| The molecular basis for the action of WNK 4 is through alteration in the membrane expression of the NaCl co transporter ( NCCT ) and the renal outer medullary K channel KCNJ 1 ( ROMK ) . ^^^ |
|
| Interacting proteins: P48048 and Q96J92 |
Pubmed |
SVM Score :0.0 |
| Most notably , the same mutations in PRKWNK 4 that relieve NCCT inhibition markedly increase inhibition of ROMK . ^^^ By expression in Xenopus laevis oocytes , we show that WNK 4 also inhibits the renal K+ channel ROMK . ^^^ This inhibition is independent of WNK 4 kinase activity and is mediated by clathrin dependent endocytosis of ROMK , mechanisms distinct from those that characterize WNK 4 inhibition of NCCT . ^^^ |
|
| Interacting proteins: P48048 and Q96J92 |
Pubmed |
SVM Score :0.0 |
| In the kidney , WNK 4 regulates the balance between NaCl reabsorption and K ( + ) secretion via variable inhibition of the thiazide sensistive NaCl cotransporter and the K ( + ) channel ROMK . ^^^ |
|
| Interacting proteins: P48048 and Q96J92 |
Pubmed |
SVM Score :0.0 |
| Although recent reports found that expression of WNK 4 in Xenopus oocytes causes inhibition of the thiazide sensitive NaCl cotransporter and the renal K channel ROMK , there may be additional targets of WNK 4 . ^^^ |
|
| Interacting proteins: P48048 and Q96J92 |
Pubmed |
SVM Score :0.0 |
| These kinases regulate ion transport across diverse epithelia ; WNK 4 reduces activity of the Na Cl cotransporter activity and the potassium channel , ROMK , by reducing their appearance at the plasma membrane . ^^^ |
|
| Interacting proteins: P48048 and Q96J92 |
Pubmed |
SVM Score :0.0 |
| The physiological studies have shown that WNK 4 downregulates the activity of ion transport pathways expressed in these nephron segments , such as the apical thiazide sensitive Na+ Cl cotransporter and apical secretory K+ channel ROMK , as well as upregulates paracellular chloride transport and phosphorylation of tight junction proteins such as claudins . ^^^ WNK 4 mutations behave as a loss of function for the Na+ Cl cotransporter and a gain of function when it comes to ROMK and claudins . ^^^ |
|
| Interacting proteins: P48048 and Q96J92 |
Pubmed |
SVM Score :0.0 |
| They have shown that , in the renal distal tubule , WNK 4 inhibits sodium reabsorption and potassium secretion , via inhibition of NCC ( thiazide sensitive Na+ Cl cotransporter ) and K+ channel ROMK activity , respectively . ^^^ |
|
| Interacting proteins: P48048 and Q96J92 |
Pubmed |
SVM Score :0.0 |
| A previous study using Xenopus oocytes showed that wild type WNK 4 expression inhibited surface expression of renal K channel ( ROMK ) and that a disease causing mutant further decreased the surface expression . ^^^ The decreased surface expression of ROMK caused by mutant WNK 4 was postulated to be a mechanism for decreased potassium secretion in distal nephrons that would presumably lead to hyperkalemia . ^^^ To determine if the mutant WNK 4 had such an inhibitory effect on the apical localization of ROMK in vivo , we generated transgenic mice using the CLCNKB gene promoter that expressed a mutant WNK 4 ( D564A ) in distal nephrons . ^^^ In both cell types , the apical localization of endogenous ROMK was not influenced by the co expression of mutant WNK 4 . ^^^ This result indicates that the mutant WNK 4 does not have a dominant effect on the cellular localization of ROMK in vivo . . ^^^ |
|
| Interacting proteins: P48048 and Q96J92 |
Pubmed |
SVM Score :0.0 |
| In oocytes expressing ROMK , wild type WNK 4 produced > 50 % inhibition of steady state current through ROMK at a +20 mV holding potential ( P < 0 . 001 ) . ^^^ Compared with wild type WNK 4 , WNK 4 564D > H causes increased cell surface expression of NCCT but reduced expression of ROMK . ^^^ This work confirms that the novel missense mutation in WNK 4 , 564D > H , is functionally active and highlights further how switching charge on a single residue in the acid motif of WNK 4 affects its interaction with the thiazide sensitive target NCCT and the potassium channel ROMK . . ^^^ |
|
| Interacting proteins: P48048 and Q96J92 |
Pubmed |
SVM Score :0.0 |
| Inhibition of ROMK by long WNK 1 was synergistic with , but not dependent on , WNK 4 . ^^^ |
|
| Interacting proteins: P48048 and Q96J92 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q96J92 and P48048 |
Pubmed |
SVM Score :0.0 |
| In the kidney , WNK 4 regulates the balance between NaCl reabsorption and K ( + ) secretion via variable inhibition of the thiazide sensistive NaCl cotransporter and the K ( + ) channel ROMK . ^^^ |
|
| Interacting proteins: Q96J92 and P48048 |
Pubmed |
SVM Score :0.0 |
| Most notably , the same mutations in PRKWNK 4 that relieve NCCT inhibition markedly increase inhibition of ROMK . ^^^ |
|
| Interacting proteins: Q96J92 and P48048 |
Pubmed |
SVM Score :0.0 |
| For example , the related kinase WNK 4 regulates the Na Cl co transporter ( NCC ) , paracellular Cl flux , and the K+ channel ROMK 1 ( Kir1 . 1 ) to maintain renal NaCl and K+ homeostasis ; mutations in PRKWNK 4 , encoding WNK 4 , cause a Mendelian disease featuring hypertension and hyperkalemia . ^^^ |
|
| Interacting proteins: Q96J92 and P48048 |
Pubmed |
SVM Score :0.0 |
| Although recent reports found that expression of WNK 4 in Xenopus oocytes causes inhibition of the thiazide sensitive NaCl cotransporter and the renal K channel ROMK , there may be additional targets of WNK 4 . ^^^ |
|
| Interacting proteins: Q96J92 and P48048 |
Pubmed |
SVM Score :0.0 |
| These kinases regulate ion transport across diverse epithelia ; WNK 4 reduces activity of the Na Cl cotransporter activity and the potassium channel , ROMK , by reducing their appearance at the plasma membrane . ^^^ |
|
| Interacting proteins: Q96J92 and P48048 |
Pubmed |
SVM Score :0.0 |
| The physiological studies have shown that WNK 4 downregulates the activity of ion transport pathways expressed in these nephron segments , such as the apical thiazide sensitive Na+ Cl cotransporter and apical secretory K+ channel ROMK , as well as upregulates paracellular chloride transport and phosphorylation of tight junction proteins such as claudins . ^^^ WNK 4 mutations behave as a loss of function for the Na+ Cl cotransporter and a gain of function when it comes to ROMK and claudins . ^^^ |
|
| Interacting proteins: Q96J92 and P48048 |
Pubmed |
SVM Score :0.0 |
| They have shown that , in the renal distal tubule , WNK 4 inhibits sodium reabsorption and potassium secretion , via inhibition of NCC ( thiazide sensitive Na+ Cl cotransporter ) and K+ channel ROMK activity , respectively . ^^^ |
|
| Interacting proteins: Q96J92 and P48048 |
Pubmed |
SVM Score :0.0 |
| A previous study using Xenopus oocytes showed that wild type WNK 4 expression inhibited surface expression of renal K channel ( ROMK ) and that a disease causing mutant further decreased the surface expression . ^^^ The decreased surface expression of ROMK caused by mutant WNK 4 was postulated to be a mechanism for decreased potassium secretion in distal nephrons that would presumably lead to hyperkalemia . ^^^ To determine if the mutant WNK 4 had such an inhibitory effect on the apical localization of ROMK in vivo , we generated transgenic mice using the CLCNKB gene promoter that expressed a mutant WNK 4 ( D564A ) in distal nephrons . ^^^ In both cell types , the apical localization of endogenous ROMK was not influenced by the co expression of mutant WNK 4 . ^^^ This result indicates that the mutant WNK 4 does not have a dominant effect on the cellular localization of ROMK in vivo . . ^^^ |
|
| Interacting proteins: Q96J92 and P48048 |
Pubmed |
SVM Score :0.0 |
| In oocytes expressing ROMK , wild type WNK 4 produced > 50 % inhibition of steady state current through ROMK at a +20 mV holding potential ( P < 0 . 001 ) . ^^^ Compared with wild type WNK 4 , WNK 4 564D > H causes increased cell surface expression of NCCT but reduced expression of ROMK . ^^^ This work confirms that the novel missense mutation in WNK 4 , 564D > H , is functionally active and highlights further how switching charge on a single residue in the acid motif of WNK 4 affects its interaction with the thiazide sensitive target NCCT and the potassium channel ROMK . . ^^^ |
|
| Interacting proteins: Q96J92 and P48048 |
Pubmed |
SVM Score :0.0 |
| Inhibition of ROMK by long WNK 1 was synergistic with , but not dependent on , WNK 4 . ^^^ |
|
| Interacting proteins: Q96J92 and P48048 |
Pubmed |
SVM Score :0.0 |
| The molecular basis for the action of WNK 4 is through alteration in the membrane expression of the NaCl co transporter ( NCCT ) and the renal outer medullary K channel KCNJ 1 ( ROMK ) . ^^^ WNK 1 affects surface expression of the ROMK potassium channel independent of WNK 4 . ^^^ |
|
| Interacting proteins: Q96J92 and P48048 |
Pubmed |
SVM Score :0.0 |
| NA |
|