1. Up-Regulation of Intestinal Phosphate Transporter NaPi-IIb (SLC34A2) by the Kinases SPAK and OSR1.
- Author
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Fezai M, Elvira B, Warsi J, Ben-Attia M, Hosseinzadeh Z, and Lang F
- Subjects
- Animals, Humans, Mice, Microinjections, Oocytes, Patch-Clamp Techniques, Phosphates metabolism, RNA administration & dosage, RNA genetics, Up-Regulation, Xenopus laevis, Intestinal Mucosa metabolism, Protein Serine-Threonine Kinases metabolism, Sodium-Phosphate Cotransporter Proteins, Type IIb biosynthesis, Sodium-Phosphate Cotransporter Proteins, Type IIb genetics
- Abstract
Background/aims: SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), kinases controlled by WNK (with-no-K[Lys] kinase), are powerful regulators of cellular ion transport and blood pressure. Observations in gene-targeted mice disclosed an impact of SPAK/OSR1 on phosphate metabolism. The present study thus tested whether SPAK and/or OSR1 contributes to the regulation of the intestinal Na(+)-coupled phosphate co-transporter NaPi-IIb (SLC34A2)., Methods: cRNA encoding NaPi-IIb was injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type SPAK, constitutively active (T233E)SPAK, WNK insensitive (T233A)SPAK, catalytically inactive (D212A)SPAK, wild-type OSR1, constitutively active (T185E)OSR1, WNK insensitive (T185A)OSR1 or catalytically inactive (D164A)OSR1. The phosphate (1 mM)-induced inward current (I(Pi)) was taken as measure of phosphate transport., Results: I(Pi) was observed in NaPi-IIb expressing oocytes but not in water injected oocytes, and was significantly increased by co-expression of SPAK, (T233E)SPAK, OSR1, (T185E)OSR1 or SPAK+OSR1, but not by co-expression of (T233A)SPAK, (D212A)SPAK, (T185A)OSR1, or (D164A)OSR1. SPAK and OSR1 both increased the maximal transport rate of the carrier., Conclusions: SPAK and OSR1 are powerful stimulators of the intestinal Na+-coupled phosphate co-transporter NaPi-IIb., (© 2015 S. Karger AG, Basel.)
- Published
- 2015
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