Jun N-terminal kinase promotes proliferation of immature erythroid cells and erythropoietin-dependent cell lines.
Erythropoietin (EPO) is the hormone necessary for development of erythrocytes from immature erythroid cells. EPO activates Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family in the EPO-dependent murine erythroid HCD57 cells. Therefore, we tested if JNK activity supported proliferation and/or survival of these cells. Treatment with the JNK inhibitor SP600125 inhibited JNK activity and EPO-dependent proliferation of HCD57 cells and the human EPO-dependent cell lines TF-1 and UT7-EPO. SP600125 also increased the fraction of cells in G2/M. Introduction of a dominant-negative form of JNK1 inhibited EPO-dependent proliferation in HCD57 cells but did not increase the fraction of cells in G2/M. Constitutive JNK activity was observed in primary murine erythroid progenitors. Treatment of primary mouse bone marrow cells with the SP600125 inhibitor reduced the number of erythroid burst-forming units (BFU-e's) but not the more differentiated erythroid colony-forming units (CFU-e's), and SP600125 protected the BFU-e's from apoptosis induced by cytosine arabinoside, demonstrating that the SP600125 inhibited proliferation of the BFU-e's. Therefore, JNK activity appears to be an important regulator of proliferation in immature, primary erythroid cells and 3 erythroid cell lines but may not be required for the survival or proliferation of CFU-e's or proerythroblasts.
Jacobs-Helber
Sarah M
SM
Department of Pharmacology/Toxicology, Virginia Commonwealth University, Richmond, USA.
Sawyer
Stephen T
ST
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003114:Colony-Forming Units Assay; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000166:cytology* / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D014162:Transfection
D000873:Anthracenes; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases