Up-Regulation of Intestinal Phosphate Transporter NaPi-IIb (SLC34A2) by the Kinases SPAK and OSR1.
OBJECTIVE
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.
Department of Physiology I, University of Tx00FC;bingen, Tx00FC;bingen, Germany.
Myriam
M
Fezai
Bernat
B
Elvira
Jamshed
J
Warsi
Mossadok
M
Ben-Attia
Zohreh
Z
Hosseinzadeh
Florian
F
Lang
D000818:Animals; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008845:Microinjections; D009865:Oocytes; D018408:Patch-Clamp Techniques; D010710:Phosphates / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012313:RNA / Q000008:administration & dosage / Q000235:genetics; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000096:biosynthesis* / Q000235:genetics*; D015854:Up-Regulation; D014982:Xenopus laevis
D010710:Phosphates; C493557:SLC34A2 protein, human; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D012313:RNA; C118135:OXSR1 protein, human; D017346:Protein Serine-Threonine Kinases; C486409:STK39 protein, human