Inhibition of Na,K-ATPase-suppressive activity of translationally controlled tumor protein by sorting nexin 6

FEBS Lett. 2006 Jun 12;580(14):3558-64. doi: 10.1016/j.febslet.2006.05.042. Epub 2006 May 24.

Abstract

Translationally controlled tumor protein (TCTP) has both extra- and intracellular functions. Our group recently reported that TCTP interacts with Na,K-ATPase and suppresses its activity. Our studies led to the identification of sorting nexin 6 (SNX6) which binds with TCTP as a potential negative regulator of TCTP. SNX6 does not interact directly with any cytoplasmic domains of Na,K-ATPase. However, when overexpressed, it restores the Na,K-ATPase activity suppressed by TCTP. This was confirmed by measurements of purified plasma membrane Na,K-ATPase activity after incubation with recombinant TCTP and SNX6. SNX6 alone has no effect on Na,K-ATPase activity, but activates Na,K-ATPase via inhibition of TCTP. Inhibition of endogenous TCTP by the overexpression of SNX6 or knockdown of TCTP expression by siTCTP increased Na,K-ATPase activity above the basal level. The interaction between SNX6 and TCTP thus appears to regulate Na,K-ATPase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Carrier Proteins / physiology*
  • DNA Primers
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Mice
  • Protein Biosynthesis / physiology*
  • Rats
  • Recombinant Proteins / metabolism
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Sorting Nexins
  • Vesicular Transport Proteins

Substances

  • Carrier Proteins
  • DNA Primers
  • Recombinant Proteins
  • SNX6 protein, human
  • Sorting Nexins
  • Vesicular Transport Proteins
  • Sodium-Potassium-Exchanging ATPase