Identification of increased protein tyrosine phosphatase activity in polycythemia vera erythroid progenitor cells.
Polycythemia vera (PV) is a clonal hematologic disease characterized by hyperplasia of the three major bone marrow lineages. PV erythroid progenitor cells display hypersensitivity to several growth factors, which might be caused by an abnormality of tyrosine phosphorylation. In the present study, we have investigated protein tyrosine phosphatase (PTP) activity in highly purified erythroid progenitor cells and found that the total PTP activity in the PV cells was twofold to threefold higher than that in normal cells. Protein separation on anion-exchange and gel-filtration columns showed that the increased activity was due to a major PTP eluted at approximately 170 kD. This enzyme was sensitive to PTP inhibitors and it did not cross-react with antibodies to SHP-1, SHP-2, or CD45. Subcellular fractionation showed that the PTP localized with the membrane fraction, where its activity was increased by threefold in PV erythroid progenitors when compared with normal cells. As the erythroid progenitors progressively matured, activity of the PTP declined rapidly in the normal cells but at a much slower rate in the PV cells. These studies suggest that a potentially novel membrane or membrane-associated PTP, representing a major PTP activity, may have an important role in proliferation and/or survival of human erythroid progenitors and that its hyperactivation in PV erythroid progenitors might be responsible for the increased erythropoiesis in PV patients.
Sui
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X
Department of Medicine, and the Department of Veterans Affairs Medical Center, Vanderbilt University, Nashville, TN 37232-6305, USA.
Krantz
S B
SB
Zhao
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Z
D000328:Adult; D000595:Amino Acid Sequence; D015415:Biomarkers / Q000097:blood; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003600:Cytosol / Q000201:enzymology; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011087:Polycythemia Vera / Q000097:blood / Q000201:enzymology*; D017027:Protein Tyrosine Phosphatases / Q000097:blood* / Q000302:isolation & purification; D012016:Reference Values; D013379:Substrate Specificity
D015415:Biomarkers; D010446:Peptide Fragments; D017027:Protein Tyrosine Phosphatases