Requirement for JAK2 in erythropoietin-induced signalling pathways.
Erythropoietin (EPO) exerts its activities by the induction of multiple signalling pathways through interaction with the erythropoietin receptor (EPOR). Previous studies have suggested that the Ras/MAP kinase as well as the JAK/STAT signalling cascades play significant roles in the induction of EPO-responsive genes. Here we show that, in HCD-57 erythroleukemic cells, both pathways are activated by EPO in a dose-dependent manner with similar sensitivities and kinetics. The activation of signalling molecules is closely related to the proliferative status of the cells. Using an antisense strategy, we were able to show that the downregulation of the JAK2 protein level in HCD-57 cells results in a distinct reduction of the ability to induce not only STAT5 DNA-binding, but also MAP kinase activity. Our results thus provide evidence for a significant contribution of the cytosolic tyrosine kinase JAK2 to the EPO-induced activation of the Ras/MAP kinase cascade.
Bittorf
T
T
Institute of Medical Biochemistry, Medical Faculty, University Rostock, Germany.
Jaster
R
R
Lüdtke
B
B
Kamper
B
B
Brock
J
J
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004921:Erythropoietin / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D053614:Janus Kinase 2; D051379:Mice; D008894:Milk Proteins; D019950:Mitogen-Activated Protein Kinase 1; D016376:Oligonucleotides, Antisense; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008894:Milk Proteins; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D004921:Erythropoietin; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse