Increased cell surface expression of C-terminal truncated erythropoietin receptors in polycythemia

Primary familial and congenital polycythemia (PFCP) is a disorder character ized by an increased number of erythrocytes despite normal blood oxygen pre ssure and a normal serum erythropoietin (EPO) level. Recent studies reveale d that erythroid progenitor cells from certain individuals with PFCP expres s various forms of EPO receptor (EPOR) truncated at the terminal carboxyl s ite (EPOR-TTC(PFCP)). EPOR-TTC(PFCP) can transmit EPO-mediated proliferativ e signals more efficiently than can full-length EPOR (EPOR-F), at least par tly because of defective recruitment of SHP-1 phosphatase to these receptor s. In agreement with previous studies, Ba/F3 transfectants expressing EPOR- TTC(PFCP) showed higher proliferative responses to EPO. In those transfecta nts, we found that EPOR-TTC(PFCP) was expressed more abundantly on the cell surface than was EPOR-F. This tendency was confirmed by a transient-expres sion experiment using COS7 cells. Since expression levels of EPOR protein w ere not significantly different among these transfectants, differences in c ell surface expression were likely dependent on post-translational mechanis m(s). In addition to defective recruitment of SHP-1 to EPOR-TTC(PFCP), snor e efficient transport and expression on the cell surface appear to serve as mechanisms responsible for increased EPO-responsiveness of erythroid proge nitor cells in PFCP.