Prenylation-dependent association of protein-tyrosine phosphatases PRL-1,-2, and-3 with the plasma membrane and the early endosome

PRL-1, -2, and -3 represent a novel class of protein-tyrosine phosphatase w ith a C-terminal prenylation motif. Although PRL-1 has been suggested to be associated with the nucleus, the presence of three highly homologous membe rs and the existence of a prenylation motif call for a more detailed examin ation of their subcellular localization. In the present study, we first dem onstrate that mouse PRL-1, -2, and -3 are indeed prenylated. Examination of N-terminal epitope-tagged PRL-1, -2, and -3 expressed in transiently trans fected cells suggests that PRL-1, -2, and -3 are present on the plasma memb rane and intracellular punctate structures. Stable Chinese hamster ovary ce lls expressing PRL-1 and -3 in an inducible manner were established. When c ells were treated with brefeldin A, PRL-1 and -3 accumulated in a collapsed compact structure around the microtubule-organizing center. Furthermore, P RL-1 and -3 redistributed into swollen vacuole-like structures when cells w ere treated with wortmannin. These characteristics of PRL-1 and -3 are typi cal for endosomal proteins. Electron microscope immunogold labeling reveals that PRL-1 and -3 are indeed associated with the plasma membrane and the e arly endosomal compartment. Expression of PRL-3 is detected in the epitheli al cells of the small intestine, where PRL-3 is present in punctate structu res in the cytoplasm. When cells are treated with FTI-277, a selective farn esyltransferase inhibitor, PRL-1, -2, and -3 shifted into the nucleus. Furt hermore, a mutant form of PRL-2 lacking the C-terminal prenylation signal i s associated with the nucleus. These results establish that the primary ass ociation of PRL-1, -2, and -3 with the membrane of the cell surface and the early endosome is dependent on their prenylation and that nuclear localiza tion of these proteins may be triggered by a regulatory event that inhibits their prenylation.