PTP-MEG2 is activated in polycythemia vera erythroid progenitor cells and is required for growth and expansion of erythroid cells.
Polycythemia vera (PV) is a human clonal hematologic disorder. Previously we demonstrated that erythroid colony-forming cells (ECFCs) from PV patients contained a hyperactive membrane-associated tyrosine phosphatase. We now show that this phosphatase corresponded to protein tyrosine phosphatase (PTP)-MEG2, an intracellular enzyme with a putative lipid-binding domain. The increased activity of PTP-MEG2 in PV cells is due to its elevated distribution in the membrane fraction. With the development of ECFCs to mature red cells, the protein level of PTP-MEG2 decreased gradually, but membrane-associated PTP-MEG2 was sustained for a longer period of time in PV cells, which correlated with an enhanced colony-forming capability of the cells. Importantly, expression of dominant-negative mutant forms of PTP-MEG2 suppressed in vitro growth and expansion of both normal and PV ECFCs. The data indicate that PTP-MEG2 has an important role in the development of erythroid cells.
Xu
Ming-Jiang
MJ
Hematology/Oncology Division, Department of Medicine, Department of Veterans Affairs Medical Center, Nashville, TN, USA.
Sui
Xingwei
X
Zhao
Runxiang
R
Dai
Chunhua
C
Krantz
Sanford B
SB
Zhao
Zhizhuang Joe
ZJ
D002455:Cell Division; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004789:Enzyme Activation; D004790:Enzyme Induction; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000201:enzymology*; D018390:Gene Targeting; D005799:Genes, Dominant; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D010766:Phosphorylation; D011087:Polycythemia Vera / Q000201:enzymology* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D011993:Recombinant Fusion Proteins / Q000502:physiology
D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C447615:PTPN9 protein, human; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor