Erythropoietin-dependent erythropoiesis: New insights and questions.
Committed erythroid progenitor cells require exposure to erythropoietin (Epo) for their survival and for their quantitatively regulated transition to red blood cells. With regard to Epo signal transduction mechanisms, much has been learned from analyses in cell line models, fetal liver or spleen-derived primary erythroblasts and human CD34pos progenitor cells from cord blood or mobilized bone marrow. Presently, we have developed an ex vivo system that efficiently supports the expansion and development of murine adult bone-marrow-derived erythroid progenitor cells. This system is outlined together with its demonstrated utility in studying (for the first time) the signaling capacities of two knocked-in phosphotyrosine-deficient Epo receptor alleles (EpoR-H and EpoR-HM). Ways in which these studies advance an understanding of core Epo signal transduction events are outlined. Also introduced are two new putative negative regulators of Epo-dependent erythropoiesis, DYRK3 and DAPK2 kinases.
Wojchowski
Don M
DM
Maine Medical Center Research Institute and Program in Stem Cell Biology and Regenerative Medicine, ME 04074-7205, USA. wojchd@mmc.org
Menon
Madhu P
MP
Sathyanarayana
Pradeep
P
Fang
Jing
J
Karur
Vinit
V
Houde
Estelle
E
Kapelle
William
W
Bogachev
Oleg
O
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D064550:Death-Associated Protein Kinases; D015672:Erythroid Precursor Cells; D004920:Erythropoiesis; D004921:Erythropoietin / Q000502:physiology*; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction; D000097603:Dyrk Kinases
D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D064550:Death-Associated Protein Kinases; D004921:Erythropoietin; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases; C579104:DAPK2 protein, human