Granulocyte macrophage-colony stimulating factor-dependent replication of polyoma virus replicon in hematopoietic cells. Analyses of receptor signals for replication and transcription.
Granulocyte macrophage-colony stimulating factor (GM-CSF) stimulates proliferation of various hematopoietic cells. Using cytoplasmic deletion mutants of the human GM-CSF receptor (hGMR) beta subunit and tyrosine kinase inhibitors, we previously showed that distinct signaling pathways of hGMR are involved in the induction of c-fos/c-jun mRNAs and of c-myc mRNA/cell proliferation. We used polyoma virus (Py) replicon to analyze the initiation of DNA replication induced by hGM-CSF in mouse BA/F3 pro-B cells expressing hGMR. hGM-CSF efficiently stimulated Py replication in the presence of Py enhancer and Py large T antigen supplied in trans. Analyses of Py enhancer mutants revealed that hGM-CSF promoted Py replication and activated transcription of the Py early promoter through the PEA3/PEBP5 region of Py enhancer. The membrane proximal region of hGMR beta subunit is required for activation of PEA3/PEBP5-dependent replication which is also required for activation of DNA synthesis in the host cells. In contrast, a more distal region which is essential for activation of c-fos and c-jun genes is required for the PEA3/PEBP5-dependent transcription of Py early promoter. These results indicate that distinct signaling pathways of hGMR are required to activate PEA3/PEBP5-dependent replication and transcription although the same enhancer is required for both activities.
Watanabe
S
S
Department of Molecular and Developmental Biology, University of Tokyo, Japan.
Ito
Y
Y
Miyajima
A
A
Arai
K
K
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects*; D004742:Enhancer Elements, Genetic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D011120:Polyomavirus / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D014779:Virus Replication / Q000187:drug effects*
D007377:Interleukin-3; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D014157:Transcription Factors; C065788:transcription factor PEA3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases