Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1242/jcs.077230 http://scihub22266oqcxt.onion/10.1242/jcs.077230 21321328!3114804!21321328     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Cell+Sci 2011 ; 124 (Pt 5): 789-800 Nephropedia Template TP {{tp|p=21321328|t=2011. Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways |pdf=|usr=}}{{21321328}} gab.com Text Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways JO: J Cell Sci http://www.kidney.de/pget.php?&tw=1&pmid=21321328 #FOAvip Ion cotransporters, such as the Na(+)/Cl(-) cotransporter (NCC), control renal salt re-absorption and are regulated by the WNK-signalling pathway, which is over-stimulated in patients suffering from Gordon's hypertension syndrome. Here, we study the regulation of the NKCC2 (SLC12A1) ion cotransporter that contributes towards ~25% of renal salt re-absorption and is inhibited by loop-diuretic hypertensive drugs. We demonstrate that hypotonic low-chloride conditions that activate the WNK1-SPAK and OSR1 pathway promote phosphorylation of NKCC2 isoforms (A, B and F) at five residues (Ser91, Thr95, Thr100, Thr105 and Ser130). We establish that the SPAK and OSR1 kinases activated by WNK interact with an RFQV motif on NKCC2 and directly phosphorylate Thr95, Thr100, Thr105 and, possibly, Ser91. Our data indicate that a SPAK-OSR1-independent kinase, perhaps AMP-activated protein kinase (AMPK), phosphorylates Ser130 and that phosphorylation of Thr105 and Ser130 plays the most important roles in stimulating NKCC2 activity. In contrast with NCC, whose membrane translocation is triggered by SPAK-OSR1 phosphorylation, NKCC2 appears to be constitutively at the membrane. Our findings provide new insights into how NKCC2 is regulated and suggest that inhibitors of SPAK and/or OSR1 for the treatment of hypertension would be therapeutically distinct from thiazide or loop diuretics, as they would suppress the activity of both NCC and NKCC2. Twit Text FOAVip Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways ????J Cell Sci http://www.kidney.de/pget.php?&tw=1&pmid=21321328 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=21321328 #FOAvip English Wikipedia <ref>{{Cite pmid|21321328}}</ref> Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways #MMPMID21321328 Richardson C; Sakamoto K; de los Heros P; Deak M; Campbell DG; Prescott AR; Alessi DR J Cell Sci 2011[Mar]; 124 (Pt 5): 789-800 PMID21321328show ga Ion cotransporters, such as the Na(+)/Cl(-) cotransporter (NCC), control renal salt re-absorption and are regulated by the WNK-signalling pathway, which is over-stimulated in patients suffering from Gordon's hypertension syndrome. Here, we study the regulation of the NKCC2 (SLC12A1) ion cotransporter that contributes towards ~25% of renal salt re-absorption and is inhibited by loop-diuretic hypertensive drugs. We demonstrate that hypotonic low-chloride conditions that activate the WNK1-SPAK and OSR1 pathway promote phosphorylation of NKCC2 isoforms (A, B and F) at five residues (Ser91, Thr95, Thr100, Thr105 and Ser130). We establish that the SPAK and OSR1 kinases activated by WNK interact with an RFQV motif on NKCC2 and directly phosphorylate Thr95, Thr100, Thr105 and, possibly, Ser91. Our data indicate that a SPAK-OSR1-independent kinase, perhaps AMP-activated protein kinase (AMPK), phosphorylates Ser130 and that phosphorylation of Thr105 and Ser130 plays the most important roles in stimulating NKCC2 activity. In contrast with NCC, whose membrane translocation is triggered by SPAK-OSR1 phosphorylation, NKCC2 appears to be constitutively at the membrane. Our findings provide new insights into how NKCC2 is regulated and suggest that inhibitors of SPAK and/or OSR1 for the treatment of hypertension would be therapeutically distinct from thiazide or loop diuretics, as they would suppress the activity of both NCC and NKCC2. |AMP-Activated Protein Kinases/metabolism[MESH] |Amino Acid Sequence[MESH] |Animals[MESH] |Cell Membrane/metabolism[MESH] |HEK293 Cells[MESH] |Humans[MESH] |Ions/metabolism[MESH] |Male[MESH] |Mice[MESH] |Mice, Inbred C57BL[MESH] |Molecular Sequence Data[MESH] |Phosphorylation[MESH] |Protein Isoforms/genetics/metabolism[MESH] |Protein Serine-Threonine Kinases/genetics/*metabolism[MESH] |Sequence Alignment[MESH] |Serine/metabolism[MESH] |Signal Transduction/physiology[MESH] |Sodium-Potassium-Chloride Symporters/genetics/*metabolism[MESH] |Solute Carrier Family 12, Member 1[MESH]Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -(epmc).pdf DeepDyve Pubget Overpricing