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Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid progenitors
- Source :
- Blood, 103, 4457-4466. American Society of Hematology, Blood, 103(12), 4457-4465. American Society of Hematology
- Publication Year :
- 2004
-
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. (Blood. 2004;103:4457-4465)
- Subjects :
- Immunology
GAB2
Biology
Biochemistry
Receptor tyrosine kinase
Cell Line
Hemoglobins
hemic and lymphatic diseases
Proto-Oncogene Proteins
Chlorocebus aethiops
Receptors, Erythropoietin
Animals
Humans
Phosphorylation
Protein kinase A
Phosphotyrosine
Protein kinase B
Erythropoietin
Adaptor Proteins, Signal Transducing
Receptor Protein-Tyrosine Kinases
Cell Differentiation
Cell Biology
Hematology
Janus Kinase 2
Protein-Tyrosine Kinases
Hematopoietic Stem Cells
Phosphoproteins
Erythropoietin receptor
Cancer research
biology.protein
Rabbits
Signal transduction
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- ISSN :
- 00064971
- Volume :
- 103
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....561461245e0281210ccba7273006d5d0