The G-CSF receptor carboxyl terminus, truncated in AML/SCN, is required for induction of a Stat5 protease activity.
Granulocyte colony-stimulating factor (G-CSF) has been shown to stimulate the activation of the signal transducer and activator of transcription 5 (Stat5). We show here that G-CSF-stimulated activation of Stat5 was attenuated when myeloid cells were induced to differentiate with G-CSF. Attenuated activation of Stat5 correlated with reduced Stat5 protein levels, which was associated with upregulation of a Stat5 protease activity. Carboxyl terminal truncation of the G-CSF receptor or expression of leukemogenic proteins Bcr-Abl and Tel-Jak2 abolished the upregulation of the Stat5 protease activity by G-CSF. These data add to our understanding of the roles of G-CSF and Stat5 in normal granulopoiesis and leukemogenesis.
Qiu
Yaling
Y
Department of Biological Sciences, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA.
Zhuang
Dazhong
D
MacRae
Alexandra
A
Dong
Fan
F
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008894:Milk Proteins / Q000235:genetics / Q000378:metabolism*; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D009503:Neutropenia / Q000151:congenital* / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor; D017384:Sequence Deletion; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D053614:Janus Kinase 2; D000097764:ETS Translocation Variant 6 Protein
D004268:DNA-Binding Proteins; D016044:Fusion Proteins, bcr-abl; D008894:Milk Proteins; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; C108603:TEL-JAK2 fusion protein, human; D053614:Janus Kinase 2; D000097764:ETS Translocation Variant 6 Protein