Inhibition of Na,K-ATPase-suppressive activity of translationally controlled tumor protein by sorting nexin 6.
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.
Yoon
Taesook
T
College of Pharmacy, Center for Cell Signaling Research and Division of Molecular Life Sciences, Ewha Woman's University, Seoul, Republic of Korea.
Kim
Moonhee
M
Lee
Kyunglim
K
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000502:physiology*; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D014176:Protein Biosynthesis / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058305:Sorting Nexins; D000090324:Tumor Protein, Translationally-Controlled 1; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D017931:DNA Primers; D011994:Recombinant Proteins; C431150:SNX6 protein, human; D058305:Sorting Nexins; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; C000715649:Tpt1 protein, rat; D000090324:Tumor Protein, Translationally-Controlled 1; D033921:Vesicular Transport Proteins; D000254:Sodium-Potassium-Exchanging ATPase