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C/EBPÁ and G-CSF receptor signals cooperate to induce the myeloperoxidase and neutrophil elastase genes
journal contribution
posted on 2001-05-01, 00:00 authored by W Wang, X Wang, Alister WardAlister Ward, I Touw, A FriedmanTo assess cooperation between G-CSF signals and C/EBP, we characterized Ba/F3 pro-B cell lines expressing C/EBPWT-ER and the G-CSF receptor (GCSFR). In these lines, GCSFR signals can be evaluated independent of their effect on C/EBP levels. G-CSF alone did not induce the MPO, NE, LF, or PU.1 RNAs, and C/EBPWT-ER alone stimulated low-level MPO and high-level PU.1 expression. Simultaneous activation of the GCSFR and C/EBPWT-ER markedly increased MPO and NE induction at 24 h, and LF mRNA was detected at 48 h. G-CSF did not increase endogenous GCSFR, endogenous C/EBP or exogenous C/EBPWT-ER levels, and C/EBPWT-ER did not induce endogenous or exogenous GCSFR. Several GCSFR mutants were also co-expressed with C/EBPWT-ER. Mutation of all four cytoplasmic tyrosines prevented NE induction but enhanced MPO induction. Mutation of Y704 was required for increased MPO induction. Consistent with this finding, removing IL-3 without G-CSF addition enabled MPO, but not NE, induction by C/EBPWT-ER. GCSFR signals or related signals from other receptors may cooperate with C/EBP to direct differentiation of normal myeloid stem cells.
History
Journal
LeukemiaVolume
15Issue
5Pagination
779 - 786Publisher
Nature Publishing GroupLocation
London, EnglandISSN
0887-6924eISSN
1476-5551Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2001, Nature Publishing GroupUsage metrics
Categories
Keywords
C\/EBPG-CSF receptorgranulopoiesishematopoiesiscytokinesScience & TechnologyLife Sciences & BiomedicineOncologyHematologyC\/EBP alphaCOLONY-STIMULATING-FACTORBINDING PROTEIN-ALPHAPROGENITOR-CELL LINEDEFICIENT MICEGRANULOCYTIC DIFFERENTIATIONTRANSCRIPTION FACTORMYELOID CELLSINCREASED APOPTOSISPU.1 SPI-132D CELLS