Int J Biochem Mol Biol 2012;3(2):242-249
Original Article
Short-term and long-term effects of protein kinase C on the trafficking and stability of
human organic anion transporter 3
Qiang Zhang*, Wonmo Suh*, Zui Pan, and Guofeng You
Department of Pharmaceutics, Rutgers, The State University of New Jersey, and Departments of Physiology and Biophysics, and
Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. *Both authors contribute equally
Received May 2, 2012; accepted May 25, 2012; Epub June 3, 2012; Published June 15, 2012
Abstract: Human organic anion transporter 3 (hOAT3) belongs to a family of organic anion transporters that play critical roles in the body
disposition of numerous clinically important drugs. Therefore, understanding the regulation of this transporter has profound clinical
significance. In the current study, we investigated the short-term and long-term regulation of hOAT3 by protein kinase C (PKC). We showed that
short-term activation of PKC by phobol 12-Myristate 13-Acetate (PMA) inhibited hOAT3 activity through accelerating its internalization from cell
surface to intracellular recycling endosomes. The colocalization of hOAT3 with EEA1-positive recycling endosomes was demonstrated by
immunolocalization with confocal microscopy. Furthermore, we showed that long-term activation of PKC resulted in the enhanced degradation
of cell surface hOAT3. The pathways for hOAT3 degradation were further examined using proteasomal and lysosomal inhibitors. Our results
showed that both proteasomal inhibitors and the lysosomal inhibitors significantly blocked hOAT3 degradation. These results demonstrate
that PKC plays critical roles in the trafficking and the stability of hOAT3. (IJBMB1205002)
Keywords: drug transporter, regulation, protein Kinase C, internalization, degradation
Address all correspondence to:
Guofeng You, PhD
Department of Pharmaceutics
Rutgers, the State University of New Jersey
160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Tel: 732-445-3831 x 218;
E-mail: gyou@rci.rutgers.edu
Original Article
Short-term and long-term effects of protein kinase C on the trafficking and stability of
human organic anion transporter 3
Qiang Zhang*, Wonmo Suh*, Zui Pan, and Guofeng You
Department of Pharmaceutics, Rutgers, The State University of New Jersey, and Departments of Physiology and Biophysics, and
Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. *Both authors contribute equally
Received May 2, 2012; accepted May 25, 2012; Epub June 3, 2012; Published June 15, 2012
Abstract: Human organic anion transporter 3 (hOAT3) belongs to a family of organic anion transporters that play critical roles in the body
disposition of numerous clinically important drugs. Therefore, understanding the regulation of this transporter has profound clinical
significance. In the current study, we investigated the short-term and long-term regulation of hOAT3 by protein kinase C (PKC). We showed that
short-term activation of PKC by phobol 12-Myristate 13-Acetate (PMA) inhibited hOAT3 activity through accelerating its internalization from cell
surface to intracellular recycling endosomes. The colocalization of hOAT3 with EEA1-positive recycling endosomes was demonstrated by
immunolocalization with confocal microscopy. Furthermore, we showed that long-term activation of PKC resulted in the enhanced degradation
of cell surface hOAT3. The pathways for hOAT3 degradation were further examined using proteasomal and lysosomal inhibitors. Our results
showed that both proteasomal inhibitors and the lysosomal inhibitors significantly blocked hOAT3 degradation. These results demonstrate
that PKC plays critical roles in the trafficking and the stability of hOAT3. (IJBMB1205002)
Keywords: drug transporter, regulation, protein Kinase C, internalization, degradation
Address all correspondence to:
Guofeng You, PhD
Department of Pharmaceutics
Rutgers, the State University of New Jersey
160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Tel: 732-445-3831 x 218;
E-mail: gyou@rci.rutgers.edu
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