Phosphatidylinositol 3-kinase regulation of fluid phase endocytosis.

Endocytosis of the fluid phase marker, horse radish peroxidase, into baby hamster kidney cells is inhibited by treatment of cells with the fungal metabolite wortmannin. The IC50 of approximately 5 nM is consistent with the well-described action of wortmannin upon phosphatidylinositol (PI) 3-kinase. Analysis of the kinetics of uptake indicates a > 50% decrease in the initial rate of marker internalisation, a concomitant decrease in the volume of the early endosome and an increased efficiency of recycling of that marker which is internalised. As PI 3-kinase binds to activated growth factor receptors our data suggest that receptor activation can be coupled to receptor internalisation (down regulation) by localising PI 3-kinase stimulation of endocytosis.