IGF-I and vanadate stimulate Na/P(i)-cotransport in OK cells by increasing type II Na/P(i)-cotransporter protein stability

Andreas W. Jehle, Judith Forgo, Jürg Biber, Eleanor Lederer, Reto Krapf, Heini Murer

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Insulin-like growth factor (IGF)-I and vanadate increase Na-dependent phosphate (Na/P(i)) cotransport in opossum kidney (OK) cells. To gain more information about the mechanisms by which IGF-I and vanadate stimulate Na/P(i)-cotransport, we measured type II Na/P(i)-cotransporter (NaPi-4) protein abundance by Western blot analysis and investigated the effects of protein synthesis and tyrosine kinase inhibitors. The key findings in the present studies are as follows. First, incubation in IGF-I (10-8 M) and/or vanadate (10-3 M) for 3 h led to a non-additive 1.4-fold increase in Na/P(i)-cotransport activity which was paralleled by a 1.5- to 2-fold increase in NaPi-4 protein. Second, actinomycin D did not abolish the increase in Na/P(i)-cotransport and cycloheximide did not prevent the IGF-I- induced increase in Na/P(i)-cotransport and NaPi-4 protein. Third, among the protein kinase inhibitors tested, only staurosporine substantially reduced the stimulation of Na/P(i)-cotransport. In conclusion, the stimulatory effect of IGF-I on Na/P(i)-cotransport is paralleled by an increased expression of NaPi-4 protein that is independent of protein synthesis and therefore results from increased protein stability. The observation that IGF-I and/or vanadate lead to similar increases in Na/P(i)-cotransport and NaPi-4 protein abundance provides further evidence that the stimulation of Na/P(i)-cotransport by IGF- I and vanadate involves protein tyrosine phosphorylation of the same signalling molecules.

Original languageEnglish (US)
Pages (from-to)149-154
Number of pages6
JournalPflugers Archiv European Journal of Physiology
Volume437
Issue number1
DOIs
StatePublished - Dec 1 1998
Externally publishedYes

Keywords

  • Opossum kidney
  • Proximal tubule
  • Renal phosphate transport
  • Tyrosine kinases

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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