Up-Regulation of Intestinal Phosphate Transporter NaPi-IIb (SLC34A2) by the Kinases SPAK and OSR1

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 T233ESPAK, WNK insensitive T233ASPAK, catalytically inactive D212ASPAK, wild-type OSR1, constitutively active T185EOSR1, WNK insensitive T185AOSR1 or catalytically inactive D164AOSR1. The phosphate (1 mM)-induced inward current (IPi) was taken as measure of phosphate transport. Results: IPi was observed in NaPi-IIb expressing oocytes but not in water injected oocytes, and was significantly increased by co-expression of SPAK, T233ESPAK, OSR1, T185EOSR1 or SPAK+OSR1, but not by co-expression of T233ASPAK, D212ASPAK, T185AOSR1, or D164AOSR1. 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.

Keywords

• Oxidative stress-responsive kinase 1
• SPS1-related proline/alanine-rich kinase
• WNK
• Phosphate
• SLC34A2