Down-regulation by Extracellular ATP of Rat Hepatocyte Organic Anion Transport Is Mediated by Serine Phosphorylation of Oatp1

摘要: Abstract Recent studies implicate a role in hepatocyte organic anion transport of plasma membrane protein that has been termed oatp1 (organic 1). Little is known regarding mechanisms by which its activity modulatedin vivo. In previous (Campbell, C. G., Spray, D. C., and Wolkoff, A. W. (1993) J. Biol. Chem. 268, 15399–15404), we demonstrated uptake sulfobromophthalein was down-regulated extracellular ATP. We have now found ATP reduces theV max for rat hepatocytes; K m remains unaltered. Reduced also results from incubation hepatocytes with the phosphatase inhibitors okadaic acid calyculin Immunoprecipitation biotinylated cell surface proteins indicates on after exposure cells to or inhibitor, suggesting loss not caused transporter internalization. Exposure of32P-loaded serine phosphorylation appearance single major tryptic phosphopeptide; control phosphorylated. This phosphopeptide comigrates one four phosphopeptides resulting acid. These indicate state must be an important consideration when assessing alterations functional expression pathobiological states.