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10.1074/jbc.RA118.003037 http://scihub22266oqcxt.onion/10.1074/jbc.RA118.003037 29921588!6078442!29921588     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Biol+Chem 2018 ; 293 (31): 12209-12221 Nephropedia Template TP {{tp|p=29921588|t=2018. C-terminally truncated, kidney-specific variants of the WNK4 kinase lack several sites that regulate its activity |pdf=|usr=}}{{29921588}} gab.com Text C-terminally truncated, kidney-specific variants of the WNK4 kinase lack several sites that regulate its activity JO: J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=29921588 #FOAvip WNK lysine-deficient protein kinase 4 (WNK4) is an important regulator of renal salt handling. Mutations in its gene cause pseudohypoaldosteronism type II, mainly arising from overactivation of the renal Na(+)/Cl(-) cotransporter (NCC). In addition to full-length WNK4, we have observed faster migrating bands (between 95 and 130 kDa) in Western blots of kidney lysates. Therefore, we hypothesized that these could correspond to uncharacterized WNK4 variants. Here, using several WNK4 antibodies and WNK4(-/-) mice as controls, we showed that these bands indeed correspond to short WNK4 variants that are not observed in other tissue lysates. LC-MS/MS confirmed these bands as WNK4 variants that lack C-terminal segments. In HEK293 cells, truncation of WNK4's C terminus at several positions increased its kinase activity toward Ste20-related proline/alanine-rich kinase (SPAK), unless the truncated segment included the SPAK-binding site. Of note, this gain-of-function effect was due to the loss of a protein phosphatase 1 (PP1)-binding site in WNK4. Cotransfection with PP1 resulted in WNK4 dephosphorylation, an activity that was abrogated in the PP1-binding site WNK4 mutant. The electrophoretic mobility of the in vivo short variants of renal WNK4 suggested that they lack the SPAK-binding site and thus may not behave as constitutively active kinases toward SPAK. Finally, we show that at least one of the WNK4 short variants may be produced by proteolysis involving a Zn(2+)-dependent metalloprotease, as recombinant full-length WNK4 was cleaved when incubated with kidney lysate. Twit Text FOAVip C-terminally truncated, kidney-specific variants of the WNK4 kinase lack several sites that regulate its activity ????J Biol Chem http://www.kidney.de/pget.php?&tw=1&pmid=29921588 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29921588 #FOAvip English Wikipedia <ref>{{Cite pmid|29921588}}</ref> C-terminally truncated, kidney-specific variants of the WNK4 kinase lack several sites that regulate its activity #MMPMID29921588 Murillo-de-Ozores AR; Rodriguez-Gama A; Bazua-Valenti S; Leyva-Rios K; Vazquez N; Pacheco-Alvarez D; De La Rosa-Velazquez IA; Wengi A; Stone KL; Zhang J; Loffing J; Lifton RP; Yang CL; Ellison DH; Gamba G; Castaneda-Bueno M J Biol Chem 2018[Aug]; 293 (31): 12209-12221 PMID29921588show ga WNK lysine-deficient protein kinase 4 (WNK4) is an important regulator of renal salt handling. Mutations in its gene cause pseudohypoaldosteronism type II, mainly arising from overactivation of the renal Na(+)/Cl(-) cotransporter (NCC). In addition to full-length WNK4, we have observed faster migrating bands (between 95 and 130 kDa) in Western blots of kidney lysates. Therefore, we hypothesized that these could correspond to uncharacterized WNK4 variants. Here, using several WNK4 antibodies and WNK4(-/-) mice as controls, we showed that these bands indeed correspond to short WNK4 variants that are not observed in other tissue lysates. LC-MS/MS confirmed these bands as WNK4 variants that lack C-terminal segments. In HEK293 cells, truncation of WNK4's C terminus at several positions increased its kinase activity toward Ste20-related proline/alanine-rich kinase (SPAK), unless the truncated segment included the SPAK-binding site. Of note, this gain-of-function effect was due to the loss of a protein phosphatase 1 (PP1)-binding site in WNK4. Cotransfection with PP1 resulted in WNK4 dephosphorylation, an activity that was abrogated in the PP1-binding site WNK4 mutant. The electrophoretic mobility of the in vivo short variants of renal WNK4 suggested that they lack the SPAK-binding site and thus may not behave as constitutively active kinases toward SPAK. Finally, we show that at least one of the WNK4 short variants may be produced by proteolysis involving a Zn(2+)-dependent metalloprotease, as recombinant full-length WNK4 was cleaved when incubated with kidney lysate. |Animals[MESH] |Kidney/chemistry/*enzymology[MESH] |Male[MESH] |Mice[MESH] |Mice, Knockout[MESH] |Organ Specificity[MESH] |Phosphorylation[MESH] |Protein Binding[MESH] |Protein Domains[MESH] |Protein Serine-Threonine Kinases/*chemistry/genetics/*metabolism[MESH]C-terminally truncated, kidney-specific variants of the WNK4 kinase la(epmc).pdf DeepDyve Pubget Overpricing