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10.1152/ajprenal.00145.2018 http://scihub22266oqcxt.onion/10.1152/ajprenal.00145.2018 29846116!6172580!29846116     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Am+J+Physiol+Renal+Physiol 2018 ; 315 (3): F734-F745 Nephropedia Template TP {{tp|p=29846116|t=2018. Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 and NCC |pdf=|usr=}}{{29846116}} gab.com Text Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 and NCC JO: Am J Physiol Renal Physiol http://www.kidney.de/pget.php?&tw=1&pmid=29846116 #FOAvip Familial hyperkalemic hypertension (FHHt) can be mainly attributed to increased activity of the renal Na(+):Cl(-) cotransporter (NCC), which is caused by altered expression and regulation of the with-no-lysine (K) 1 (WNK1) or WNK4 kinases. The WNK1 gene gives rise to a kidney-specific isoform that lacks the kinase domain (KS-WNK1), the expression of which occurs primarily in the distal convoluted tubule. The role played by KS-WNK1 in the modulation of the WNK/STE20-proline-alanine rich kinase (SPAK)/NCC pathway remains elusive. In the present study, we assessed the effect of human KS-WNK1 on NCC activity and on the WNK4-SPAK pathway. Microinjection of oocytes with human KS-WNK1 cRNA induces remarkable activation and phosphorylation of SPAK and NCC. The effect of KS-WNK1 was abrogated by eliminating a WNK-WNK-interacting domain and by a specific WNK inhibitor, WNK463, indicating that the activation of SPAK/NCC by KS-WNK1 is due to interaction with another WNK kinase. Under control conditions in oocytes, the activating serine 335 of the WNK4 T loop is not phosphorylated. In contrast, this serine becomes phosphorylated when the intracellular chloride concentration ([Cl(-)](i)) is reduced or when KS-WNK1 is coexpressed with WNK4. KS-WNK1-mediated activation of WNK4 is not due to a decrease of the [Cl(-)](i). Coimmunoprecipitation analysis revealed that KS-WNK1 and WNK4 interact with each other and that WNK4 becomes autophosphorylated at serine 335 when it is associated with KS-WNK1. Together, these observations suggest that WNK4 becomes active in the presence of KS-WNK1, despite a constant [Cl(-)](i). Twit Text FOAVip Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 and NCC ????Am J Physiol Renal Physiol http://www.kidney.de/pget.php?&tw=1&pmid=29846116 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29846116 #FOAvip English Wikipedia <ref>{{Cite pmid|29846116}}</ref> Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 and NCC #MMPMID29846116 Argaiz ER; Chavez-Canales M; Ostrosky-Frid M; Rodriguez-Gama A; Vazquez N; Gonzalez-Rodriguez X; Garcia-Valdes J; Hadchouel J; Ellison D; Gamba G Am J Physiol Renal Physiol 2018[Sep]; 315 (3): F734-F745 PMID29846116show ga Familial hyperkalemic hypertension (FHHt) can be mainly attributed to increased activity of the renal Na(+):Cl(-) cotransporter (NCC), which is caused by altered expression and regulation of the with-no-lysine (K) 1 (WNK1) or WNK4 kinases. The WNK1 gene gives rise to a kidney-specific isoform that lacks the kinase domain (KS-WNK1), the expression of which occurs primarily in the distal convoluted tubule. The role played by KS-WNK1 in the modulation of the WNK/STE20-proline-alanine rich kinase (SPAK)/NCC pathway remains elusive. In the present study, we assessed the effect of human KS-WNK1 on NCC activity and on the WNK4-SPAK pathway. Microinjection of oocytes with human KS-WNK1 cRNA induces remarkable activation and phosphorylation of SPAK and NCC. The effect of KS-WNK1 was abrogated by eliminating a WNK-WNK-interacting domain and by a specific WNK inhibitor, WNK463, indicating that the activation of SPAK/NCC by KS-WNK1 is due to interaction with another WNK kinase. Under control conditions in oocytes, the activating serine 335 of the WNK4 T loop is not phosphorylated. In contrast, this serine becomes phosphorylated when the intracellular chloride concentration ([Cl(-)](i)) is reduced or when KS-WNK1 is coexpressed with WNK4. KS-WNK1-mediated activation of WNK4 is not due to a decrease of the [Cl(-)](i). Coimmunoprecipitation analysis revealed that KS-WNK1 and WNK4 interact with each other and that WNK4 becomes autophosphorylated at serine 335 when it is associated with KS-WNK1. Together, these observations suggest that WNK4 becomes active in the presence of KS-WNK1, despite a constant [Cl(-)](i). |Animals[MESH] |Chlorides/*metabolism[MESH] |Enzyme Activation[MESH] |Female[MESH] |Humans[MESH] |Kidney/*enzymology[MESH] |Oocytes[MESH] |Phosphorylation[MESH] |Protein Serine-Threonine Kinases/genetics/*metabolism[MESH] |Rats[MESH] |Sodium/*metabolism[MESH] |Solute Carrier Family 12, Member 3/genetics/metabolism[MESH] |WNK Lysine-Deficient Protein Kinase 1/genetics/*metabolism[MESH] |Xenopus Proteins/metabolism[MESH]Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 a(epmc).pdf DeepDyve Pubget Overpricing