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Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid progenitors

Item Type:Article
Title:Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid progenitors
Creators Name:van den Akker, E. and van Dijk, T. and Parren-van Amelsvoort, M. and Grossmann, K.S. and Schaeper, U. and Toney-Earley, K. and Waltz, S.E. and Loewenberg, B. and von Lindern, M.
Abstract:Erythropoietin (EPO) is required for cell survival during differentiation and for progenitor expansion during stress erythropoiesis. Although signaling pathways may couple directly to docking sites on the EPO receptor (EpoR), additional docking molecules expand the signaling platform of the receptor. We studied the roles of the docking molecules Grb2-associated binder-1 (Gab1) and Gab2 in EPO-induced signal transduction and erythropoiesis. Inhibitors of phosphatidylinositide 3-kinase and Src kinases suppressed EPO-dependent phosphorylation of Gab2. In contrast, Gab1 activation depends on recruitment and phosphorylation by the tyrosine kinase receptor RON, with which it is constitutively associated. RON activation induces the phosphorylation of Gab1, mitogen-activated protein kinase (MAPK), and protein kinase B (PKB) but not of signal transducer and activator of transcription 5 (Stat5). RON activation was sufficient to replace EPO in progenitor expansion but not in differentiation. In conclusion, we elucidated a novel mechanism specifically involved in the expansion of erythroblasts involving RON as a downstream target of the EpoR.
Keywords:Cell Differentiation, Cell Line, Cercopithecus aethiops, Erythropoietin, Erythropoietin Receptors, Hematopoietic Stem Cells, Hemoglobins, Janus Kinase 2, Phosphoproteins, Phosphorylation, Phosphotyrosine, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, Signal Transducing Adaptor Proteins, Animals, Rabbits
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Volume:103
Number:12
Page Range:4457-4465
Date:1 January 2004
Official Publication:https://doi.org/10.1182/blood-2003-08-2713
PubMed:View item in PubMed

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