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p38 MAP Kinase Inhibits Neutrophil Development Through Phosphorylation of C/EBPα on Serine 21 by Christian R. Geest; Miranda Buitenhuis; Annemieke G. Laarhoven; Marc B. Bierings; Marrie C.A. Bruin; Edo Vellenga; Paul J. Coffer is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
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## Abstract Many extracellular stimuli regulate growth, survival, and differentiation responses through activation of the dual specificity mitogen activated protein kinase (MAPK) kinase three (MKK3) and its downstream effector p38 MAPK. Using CD34+ hematopoietic progenitor cells, here we describe a novel role for MKK3-p38MAPK in the regulation of myelopoiesis. Inhibition of p38MAPK utilizing the pharmacological inhibitor SB203580, enhanced neutrophil development ex vivo, but conversely reduced eosinophil differentiation. In contrast, constitutive activation of MKK3 dramatically inhibited neutrophil differentiation. Transplantation of β2-microglobulin−/− nonobese diabetic/severe combined immune deficient (NOD/SCID) mice with CD34+ cells ectopically expressing constitutively active MKK3 resulted in reduced neutrophil differentiation in vivo, whereas eosinophil development was enhanced. Inhibitory phosphorylation of CCAAT/enhancer binding protein α (C/EBPα) on serine 21 was induced upon activation of p38MAPK. Moreover, ectopic expression of a non-phosphorylatable C/EBPα mutant was sufficient to abrogate MKK3-induced inhibition of neutrophil development. Furthermore, treatment of CD34+
Who reads p38 MAP Kinase Inhibits Neutrophil Development Through Phosphorylation of C/EBPα on Serine 21?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Christian R. Geest; Miranda Buitenhuis; Annemieke G. Laarhoven; Marc B. Bierings; Marrie C.A. Bruin; Edo Vellenga; Paul J. Coffer
- Publisher
- Oxford University Press (OUP)
- Published
- 2009
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)