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J Am Soc Nephrol
2011 May 01;225:873-80. doi: 10.1681/ASN.2010070757.
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PKB/SGK-resistant GSK3 enhances phosphaturia and calciuria.
Föller M, Kempe DS, Boini KM, Pathare G, Siraskar B, Capuano P, Alesutan I, Sopjani M, Stange G, Mohebbi N, Bhandaru M, Ackermann TF, Judenhofer MS, Pichler BJ, Biber J, Wagner CA, Lang F.
???displayArticle.abstract??? Insulin and IGF1-dependent signaling activates protein kinase B and serum and glucocorticoid inducible kinase (PKB/SGK), which together phosphorylate and inactivate glycogen synthase kinase GSK3. Because insulin and IGF1 increase renal tubular calcium and phosphorus reabsorption, we examined GSK3 regulation of phosphate transporter activity and determined whether PKB/SGK inactivates GSK3 to enhance renal phosphate and calcium transport. Overexpression of GSK3 and the phosphate transporter NaPi-IIa in Xenopus oocytes decreased electrogenic phosphate transport compared with NaPi-IIa-expressing oocytes. PKB/SGK serine phosphorylation sites in GSK3 were mutated to alanine to create gsk3(KI) mice resistant to PKB/SGK inactivation. Compared with wildtype animals, gsk3(KI) animals exhibited greater urinary phosphate and calcium clearances with higher excretion rates and lower plasma concentrations. Isolated brush border membranes from gsk3(KI) mice showed less sodium-dependent phosphate transport and Na-phosphate co-transporter expression. Parathyroid hormone, 1,25-OH vitamin D levels, and bone mineral density were decreased in gsk3(KI) mice, suggesting a global dysregulation of bone mineral metabolism. Taken together, PKB/SGK phosphorylation of GSK3 increases phosphate transporter activity and reduces renal calcium and phosphate loss.
Allon,
Effects of insulin and glucose on renal phosphate reabsorption: interactions with dietary phosphate.
1992, Pubmed
Allon,
Effects of insulin and glucose on renal phosphate reabsorption: interactions with dietary phosphate.
1992,
Pubmed Bacic,
The renal Na+/phosphate cotransporter NaPi-IIa is internalized via the receptor-mediated endocytic route in response to parathyroid hormone.
2006,
Pubmed Bacic,
Involvement of the MAPK-kinase pathway in the PTH-mediated regulation of the proximal tubule type IIa Na+/Pi cotransporter in mouse kidney.
2003,
Pubmed Biber,
Isolation of renal proximal tubular brush-border membranes.
2007,
Pubmed Biber,
Regulation of phosphate transport in proximal tubules.
2009,
Pubmed Biber,
A high yield preparation for rat kidney brush border membranes. Different behaviour of lysosomal markers.
1981,
Pubmed Boehmer,
The peptide transporter PEPT2 is targeted by the protein kinase SGK1 and the scaffold protein NHERF2.
2008,
Pubmed
,
Xenbase Boehmer,
Modulation of the voltage-gated potassium channel Kv1.5 by the SGK1 protein kinase involves inhibition of channel ubiquitination.
2008,
Pubmed
,
Xenbase Boini,
Steroid hormone release as well as renal water and electrolyte excretion of mice expressing PKB/SGK-resistant GSK3.
2008,
Pubmed Boros,
Active Ca(2+) reabsorption in the connecting tubule.
2009,
Pubmed Brown,
Differential effects of 19-nor-1,25-dihydroxyvitamin D(2) and 1,25-dihydroxyvitamin D(3) on intestinal calcium and phosphate transport.
2002,
Pubmed Busch,
Properties of electrogenic Pi transport by a human renal brush border Na+/Pi transporter.
1995,
Pubmed
,
Xenbase Chaudhary,
The cell survival signal Akt is differentially activated by PDGF-BB, EGF, and FGF-2 in osteoblastic cells.
2001,
Pubmed Cohen,
GSK3 inhibitors: development and therapeutic potential.
2004,
Pubmed Cross,
The role of Na+/K+ ATPase activity during low flow ischemia in preventing myocardial injury: a 31P, 23Na and 87Rb NMR spectroscopic study.
1995,
Pubmed Custer,
Expression of Na-P(i) cotransport in rat kidney: localization by RT-PCR and immunohistochemistry.
1994,
Pubmed DeFronzo,
The effects of glucose and insulin on renal electrolyte transport.
1976,
Pubmed DeFronzo,
The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man.
1975,
Pubmed Feld,
Insulinlike growth factor I and the kidney.
1996,
Pubmed Friedman,
Mechanisms of renal calcium transport.
2000,
Pubmed Hawkins,
Signalling through Class I PI3Ks in mammalian cells.
2006,
Pubmed Hoenderop,
Calcium absorption across epithelia.
2005,
Pubmed Hoskins,
Evidence for a direct action of insulin to increase renal reabsorption of calcium and for an irreversible defect in renal ability to conserve calcium due to prolonged absence of insulin.
1984,
Pubmed Jehle,
IGF-I and vanadate stimulate Na/Pi-cotransport in OK cells by increasing type II Na/Pi-cotransporter protein stability.
1998,
Pubmed Kanatani,
Effect of high phosphate concentration on osteoclast differentiation as well as bone-resorbing activity.
2003,
Pubmed Kato,
Genetic mutation in the human 25-hydroxyvitamin D3 1alpha-hydroxylase gene causes vitamin D-dependent rickets type I.
1999,
Pubmed Kwak,
AG490, a Jak2-specific inhibitor, induces osteoclast survival by activating the Akt and ERK signaling pathways.
2008,
Pubmed Lang,
(Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms.
2006,
Pubmed Lee,
Tumor necrosis factor-alpha supports the survival of osteoclasts through the activation of Akt and ERK.
2001,
Pubmed Martin,
Acute regulation of parathyroid hormone by dietary phosphate.
2005,
Pubmed McManus,
Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis.
2005,
Pubmed Murer,
Proximal tubular phosphate reabsorption: molecular mechanisms.
2000,
Pubmed Murer,
The sodium phosphate cotransporter family SLC34.
2004,
Pubmed Nowik,
Renal phosphaturia during metabolic acidosis revisited: molecular mechanisms for decreased renal phosphate reabsorption.
2008,
Pubmed Perwad,
Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice.
2005,
Pubmed Picard,
Acute parathyroid hormone differentially regulates renal brush border membrane phosphate cotransporters.
2010,
Pubmed Portale,
Human 25-hydroxyvitamin D-1alpha-hydroxylase: cloning, mutations, and gene expression.
2000,
Pubmed Sakoda,
Differing roles of Akt and serum- and glucocorticoid-regulated kinase in glucose metabolism, DNA synthesis, and oncogenic activity.
2003,
Pubmed Shaw,
Further evidence that the inhibition of glycogen synthase kinase-3beta by IGF-1 is mediated by PDK1/PKB-induced phosphorylation of Ser-9 and not by dephosphorylation of Tyr-216.
1997,
Pubmed Strutz-Seebohm,
PIKfyve in the SGK1 mediated regulation of the creatine transporter SLC6A8.
2007,
Pubmed
,
Xenbase Vallon,
In vivo studies of the genetically modified mouse kidney.
2003,
Pubmed Villa-Bellosta,
The Na+-Pi cotransporter PiT-2 (SLC20A2) is expressed in the apical membrane of rat renal proximal tubules and regulated by dietary Pi.
2009,
Pubmed Woudenberg-Vrenken,
The role of transient receptor potential channels in kidney disease.
2009,
Pubmed Wyatt,
DOCA-induced phosphorylation of glycogen synthase kinase 3beta.
2006,
Pubmed
