Regulation of protein sorting at the TGN by plasma membrane receptor activation

We show that in the rat basophilic leukemia cell line RBL, the physiologica l stimulation of the IgE receptor or direct activation of PKC leads to the missorting of proteins to the plasma membrane, diverting them from their no rmal intracellular destination. This is demonstrated for two classes of pro teins that are normally targeted to the secretory lysosomes via completely different mechanisms, i,e. proteoglycans and the aspartic protease cathepsi n D, In the latter case, normal processing of the enzyme is also affected, leading to secretion of the immature form of cathepsin, The present study s hows how completely different sorting mechanisms, such as those for deliver ing proteoglycans and cathepsin D to secretory lysosomes, might share commo n regulatory signals and are similarly affected when the levels of these si gnals are perturbed. Finally, protein kinase C appears to be a major player in the signal transduction pathways, leading to proteoglycan and cathepsin D missorting.