Vanadate mimics the effect of stem cell factor on highly purified human erythroid burst-forming units in vitro, but not the effect of erythropoietin.
When orthovanadate, an inhibitor of protein tyrosine phosphatase activity, was added to highly purified human blood erythroid burst-forming units (BFU-E) a marked increase in the number and size of erythroid bursts was evident at an optimum concentration of 4 microM. Because BFU-E are stimulated by stem cell factor (SCF), interleukin 3 (IL-3), and erythropoietin (EP), this effect could occur through an enhancement of any one of these pathways. However, no effect was observed on human erythroid colony-forming units (CFU-E), indicating that vanadate was not potentiating the effect of EP. The time course of decline in BFU-E, when vanadate was added in vitro on successive days, followed the time course produced by delayed addition of SCF but not IL-3. In addition, vanadate markedly enhanced the effect of an optimal concentration of IL-3, but it could only enhance the effect of SCF when SCF concentrations were less than optimum. These experiments demonstrate that vanadate markedly stimulates the number and size of human BFU-E in vitro and that it mimics the effect of SCF. Vanadate may be acting as a phosphatase inhibitor that potentiates the kinase activity induced by SCF, but elucidation of its specific biochemical effects on these cells awaits further investigation.
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects*; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology; D004921:Erythropoietin / Q000494:pharmacology*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D019089:Stem Cell Factor; D013997:Time Factors; D014638:Vanadates / Q000494:pharmacology*
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D019089:Stem Cell Factor; D004921:Erythropoietin; D014638:Vanadates