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Polycythemia vera. V. Enhanced proliferation and phosphorylation due to
vanadate are diminished in polycythemia vera erythroid progenitor cells: a
possible defect of phosphatase activity in polycythemia vera
CH Dai, SB Krantz and ST Sawyer
Department of Medicine, Department of Veterans Affairs Medical Center,
Vanderbilt University School of Medicine, Nashville, TN 37232-6305, USA.
Erythropoietin (EP) and stem cell factor (SCF) are essential growth factors
for erythroid progenitor cell proliferation and differentiation in
serum-free culture. It has been previously shown that burst-forming
units-erythroid and colony-forming units-erythroid from patients with
polycythemia vera (PV) have enhanced sensitivity to EP and SCF compared
with normal erythroid progenitors, but little is known about the mechanism
for this difference. In the present investigation, the effect of EP and SCF
on protein tyrosine phosphorylation in day-8 normal and PV erythroid
colony-forming cells, which give rise to colonies of 2-49 hemoglobinized
cells, was studied. EP rapidly induced tyrosine phosphorylation of the EP
receptor, whereas the most prominent phosphorylated protein induced by SCF
was identified as the SCF receptor. No additional phosphorylated proteins
were evident when PV cells were compared with normal cells. Culture of
normal erythroid progenitors with orthovanadate, an inhibitor of protein
tyrosine phosphatases, resulted in an increased number of erythroid
colonies and enhanced protein tyrosine phosphorylation. However, in
contrast, little enhancement was evident with PV cells. These results
indicate that, although vanadate may be acting in normal erythroid
progenitors as a phosphatase inhibitor that potentiates the kinase activity
induced by SCF and EP, this function is diminished in PV cells. Because
erythropoiesis is regulated by a balance between protein tyrosine kinase
activity and protein tyrosine phosphatase activity, PV patients may have an
abnormal phosphatase activity allowing increased cell proliferation.
Volume 89,
Issue 10,
pp. 3574-3581,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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