title: Stimulation of Na(+) coupled phosphate transporter NaPiIIa by janus kinase JAK2.
abstract: BACKGROUND
  Na(+) coupled phosphate transporter NaPiIIa is the main carrier accomplishing phosphate transport across the apical cell membrane of proximal renal tubules and thus renal tubular phosphate reabsorption. The carrier is regulated by a wide variety of hormones and cellular signaling molecules. Hormones stimulating renal tubular phosphate transport and thus leading to hyperphosphatemia include growth hormone. Signaling of growth hormone involves activation of janus-activated kinase-2 JAK2, which has previously been shown to participate in the regulation of several Na(+) coupled transporters. Experiments exploring the effect of JAK2 on phosphate transport have, however, never been reported. The present study thus addressed the effect of JAK2 on NaPiIIa.
  
  
  METHODS
  cRNA encoding NaPiIIa was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild type JAK2, the gain of function mutant JAK2(V617F) or inactive JAK2(K882E). Phosphate-induced current (I(NaPi)) reflecting electrogenic phosphate transport was determined by two electrode voltage clamp. Moreover, NaPiIIa protein abundance in the cell membrane was determined by chemiluminescence.
  
  
  RESULTS
  No appreciable I(NaPi) was observed in water injected oocytes or in oocytes expressing JAK2 alone. In NaPiIIa expressing oocytes I(NaPi) was significantly increased by additional expression of JAK2 or JAK2(V617F), but not by coexpression of JAK2(K882E). In oocytes expressing both, NaPiIIa and JAK2, I(NaPi) was gradually decreased by JAK2 inhibitor AG490 (40 μM). Coexpression of NaPiIIa and JAK2 or JAK2(V617F), but not of JAK2(K882E) increased NaPiIIa protein abundance in the cell membrane. Disruption of carrier protein insertion with Brefeldin A (5 μM) was followed by a decline of I(NaPi) to a similar extent in Xenopus oocytes expressing NaPiIIa with JAK2 and in Xenopus oocytes expressing NaPiIIa alone, suggesting that JAK2 did not affect carrier stability in the cell membrane.
  
  
  CONCLUSIONS
  JAK2 contributes to the regulation of phosphate transporter NaPiIIa.
authors: Department of Physiology 1, University of Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.
authors: Manzar
authors: M
authors: Shojaiefard
authors: Zohreh
authors: Z
authors: Hosseinzadeh
authors: Tatsiana
authors: T
authors: Pakladok
authors: Shefalee K
authors: SK
authors: Bhavsar
authors: Florian
authors: F
authors: Lang
mesh_terms: D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D006801:Humans; D017136:Ion Transport; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes; D010710:Phosphates / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000819:agonists*; D014981:Xenopus
chemical_list: D010710:Phosphates; C493554:SLC34A1 protein, human; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D012964:Sodium; C507924:JAK2 protein, human; D053614:Janus Kinase 2