Up-regulation of the Pit-2 phosphate transporter/retrovirus receptor by protein kinase C ε

Zsolt Jobbagy, Zoltan Olah, Gyorgy Petrovics, Maribeth V. Eiden, Betsy D. Leverett, Nicholas M. Dean, Wayne B. Anderson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


The membrane receptors for the gibbon ape leukemia retrovirus and the amphotropic murine retrovirus serve normal cellular functions as sodium- dependent phosphate transporters (Pit-1 and Pit-2, respectively). Our earlier studies established that activation of protein kinase C (PKC) by treatment of cells with phorbol 12-myristate 13-acetate (PMA) enhanced sodium-dependent phosphate (Na/P(i)) uptake. Studies now have been carried out to determine which type of Na/P(i) transporter (Pit-1 or Pit-2) is regulated by PKC and which PKC isotypes are involved in the up-regulation of Na/P(i) uptake by the Na/P(i) transporter/viral receptor. It was found that the activation of short term (2-min) Na/P(i) uptake by PMA is abolished when cells are infected with amphotropic murine retrovirus (binds Pit-2 receptor) but not with gibbon ape leukemia retrovirus (binds Pit-1 receptor), indicating that Pit-2 is the form of Na/P(i) transporter/viral receptor regulated by PKC. The PKC-mediated activation of Pit-2 was blocked by pretreating cells with the pan-PKC inhibitor bisindolylmaleimide but not with the conventional PKC isotype inhibitor Go 6976, suggesting that a novel PKC isotype is required to regulate Pit-2. Overexpression of PKCε, but not of PKCα, -δ, or -ζ, was found to mimic the activation of Na/P(i) uptake. To further establish that PKCε is involved in the regulation of Pit-2, cells were treated with PKCε- selective antisense oligonucleotides. Treatment with PKCε antisense oligonucleotides decreased the PMA-induced activation of Na/P(i) uptake. These results indicate that PMA-induced stimulation of Na/P(i) uptake by Pit- 2 is specifically mediated through activation of PKCε.

Original languageEnglish
Pages (from-to)7067-7071
Number of pages5
JournalJournal of Biological Chemistry
Issue number11
StatePublished - 12 Mar 1999
Externally publishedYes


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