Protein kinase C affects transport function of organic anion transporting polypeptide 1B1 (1141.7)

Abstract

Objective: Organic anion transporting polypeptides (OATPs) are a family of important uptake transporters. It was demonstrated previously that OATP uptake function is regulated by protein kinase C (PKC). However, the phosphorylation site(s) modified involved in PKC regulation remains unknown. Methods: HEK293 cells stably expressing organic anion transporting polypeptides 1B1 (OATP1B1) were treated by PKC modulators to investigate its regulatory effect on OATP1B1. In addition, site‐directed mutagenesis was used to identify the possible PKC regulation sites within OATP1B1. Results: We found out that OATP1B1 uptake function is regulated by PKC modulators. Further studies indicated that PKC may affect OATP1B1 activity through its regulation of the protein expression on the cell surface. Moreover, we found out that PKC activator PMA not only affect the internalization of OATP1B1 but its recycling as well. Mutagenesis studies revealed that several amino acids located at intracellular loops and the carboxyl terminus of OATP1B1 are involved in the phosphorylation regulation process. Conclusions: OATP1B1 transport function is regulated by PKC, the action of which leads to accelerated internalization and reduced recycling of the transporter protein.Grant Funding Source: Supported by National Natural Science Foundation of China Grant #81373473 and #U1332124