Table of Contents
Journal of Signal Transduction
Volume 2011 (2011), Article ID 860985, 7 pages
http://dx.doi.org/10.1155/2011/860985
Review Article

Involvement of Phosphatases in Proliferation, Maturation, and Hemoglobinization of Developing Erythroid Cells

Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel

Received 1 February 2011; Revised 11 April 2011; Accepted 4 May 2011

Academic Editor: David Leitenberg

Copyright © 2011 Eitan Fibach. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Production of RBCs is triggered by the action of erythropoietin (Epo) through its binding to surface receptors (Epo-R) on erythroid precursors in the bone marrow. The intensity and the duration of the Epo signal are regulated by several factors, including the balance between the activities of kinesase and phosphatases. The Epo signal determines the proliferation and maturation of the precursors into hemoglobin (Hb)-containing RBCs. The activity of various protein tyrosine phosphatases, including those involved in the Epo pathway, can be inhibited by sodium orthovanadate (Na3VO4, vanadate). Adding vanadate to cultured erythroid precursors of normal donors and patients with β-thalassemia enhanced cell proliferation and arrested maturation. This was associated with an increased production of fetal hemoglobin (HbF). Increased HbF in patients with β-hemoglobinopathies (β-thalassemia and sickle cell disease) ameliorates the clinical symptoms of the disease. These results raise the possibility that specific and nontoxic inhibitors of phosphatases may be considered as a therapeutic modality for elevating HbF in patients with β-hemoglobinopathies as well as for intensifying the Epo response in other forms of anemia.