title: Increased cell surface expression of C-terminal truncated erythropoietin receptors in polycythemia.
abstract: Primary familial and congenital polycythemia (PFCP) is a disorder characterized by an increased number of erythrocytes despite normal blood oxygen pressure and a normal serum erythropoietin (EPO) level. Recent studies revealed that erythroid progenitor cells from certain individuals with PFCP express various forms of EPO receptor (EPOR) truncated at the terminal carboxyl site (EPOR-TTC(PFCP)). EPOR-TTC(PFCP) can transmit EPO-mediated proliferative signals more efficiently than can full-length EPOR (EPOR-F), at least partly because of defective recruitment of SHP-1 phosphatase to these receptors. In agreement with previous studies, Ba/F3 transfectants expressing EPOR-TTC(PFCP) showed higher proliferative responses to EPO. In those transfectants, 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-expression experiment using COS7 cells. Since expression levels of EPOR protein were not significantly different among these transfectants, differences in cell surface expression were likely dependent on post-translational mechanism(s). In addition to defective recruitment of SHP-1 to EPOR-TTC(PFCP), more efficient transport and expression on the cell surface appear to serve as mechanisms responsible for increased EPO-responsiveness of erythroid progenitor cells in PFCP.
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba and CREST (JST), Tsukuba, Ibaraki, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Motohashi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Osawa
authors.forename: T
authors.initials: T
authors.lastname: Hiroyama
authors.forename: A
authors.initials: A
authors.lastname: Iwama
authors.forename: A
authors.initials: A
authors.lastname: Shibuya
authors.forename: H
authors.initials: H
authors.lastname: Nakauchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics; D015672:Erythroid Precursor Cells / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D011086:Polycythemia / Q000235:genetics; D016133:Polymerase Chain Reaction; D021381:Protein Transport; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D017467:Receptors, Erythropoietin / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D017467:Receptors, Erythropoietin; D011993:Recombinant Fusion Proteins; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse